DESC:FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of a Tryptophol intermediate of the formula (I)
Formula (I)

where R represents alkyl, aryl, aralkyl, substituted alkyl, hydroxyl, alkoxy, halogen group.
The present invention specifically relates to an improved process for the preparation of 7- Ethyl Tryptophol having the Formula (Ia)
Formula (Ia)

or its salts.
The present invention also relates to a process for the preparation of 2-substituted phenyl hydrazine having the Formula (II)
Formula (II)

or its salts where R is as defined earlier, useful in the preparation of compound of Formula (I).
The present invention also relates to a process for the preparation of 2-ethylphenyl hydrazine having the Formula (IIa)
Formula (IIa)

or its salts useful in the preparation of compound of Formula (Ia).

BACKGROUND OF THE INVENTION
2-ethyl phenyl hydrazine hydrochloride is the key starting material for the preparation of 7-ethyl tryptophol. The 2-ethyl phenyl hydrazine hydrochloride preparation has been reported by several methods. One is the reaction of 2- ethyl aniline prepare a diazonium salt with sodium nitrite and conc. Hydrochloric acid followed by reduction of the diazonium salt with expensive tin chloride. The other method is the reduction of the diazonium salt with sodium sulphite using base (sodium hydroxide) and with Sulfuric acid. The reaction is generally carried out in water. While preparing the title compound by the reported method, the inventors of the present invention observed inconsistency in the process, low purity and low yield, formation of various impurities and tedious work-up.
7- Ethyl Tryptophol (7-ET) preparation has been reported by several methods. One is the reaction of 2-ethylaniline with 2,2,2-trichloroethane-1,1-diol gave the corresponding aldehyde which on further treatment with hydroxylamine hydrochloride obtained 7-ethylisatin. This intermediate is elaborated to final product, 7-ethyl tryptophol in three steps via 7-ethyl-3-indolylglyoxylate. This process is disclosed in Cephalon’s US 7,446,122 B2.
US 4,585,877 A discloses a process for the formation of 7-ET by Fischer indole synthesis from 2-ethylphenylhydrazine hydrochloride and dihydrofuran (DHF) using dioxane and water and the product formed as oil, which is flash chromatographed to give the final 7-ET.
WO 1999/059970 A1 discloses a process for the formation of 7-ET by reacting 2 ,3-dihydrofuran and the aryl hydrazine which is carried out in an ethereal solvent which is miscible in water, for example, tetrahydrofuran (THF), glyme, diglyme or 1,4-dioxane.
Unfortunately the reaction described in the above prior-art references produces a lot of side products and 7-ET is generally isolated from the reaction as a tarry solid or sticky oil in poor yields (less than 50%) and requires column chromatography for purification.
A related strategy for the one-pot synthesis of various tryptophol and tryptophol homologues by a Fischer indole synthesis was described in Org. Lett. 2004, 6, 79-82. Substituted phenylhydrazine hydrochlorides were mixed with cyclic enol ethers in DMA/H2O as solvent in the presence of sulfuric acid. The hydrazones were formed in situ from the hydrazine hydrochloride and the enol ether, and the ensuing [3,3]-rearrangement of the respective ene-hydrazine at 100 °C provided 3-substituted indoles in good yields after chromatography. The major side product was the adduct, which evidently is derived from a further reaction of the indole product with unconsumed enol ether which is shown in the scheme given below:

Several subsequent papers (Tetrahedron Letters 49 (2008) 3335–3340) have described modifications of this protocol, such as the use of Montmorillonite-K10 or mesoporous MCM-41 as heterogeneous catalysts. It was argued that the use of heterogeneous catalysts reduces dimerization and polymerization of the tryptophol owing to the shape and size selectivity of these catalysts.
This present invention describes an economical and scalable improved process for the synthesis of 2-ethyl phenyl hydrazine hydrochloride and 7-Ethyl tryptophol, a key intermediate of Etodolac. Other substituted Tryptophol’s are used in the preparation of several drug products. Etodolac is a non-steroidal anti-inflammatory drug (NSAID). The product was approved for medical use in 1985. It was approved in the U.S. in 1991.
NSAIDs are used for the management of mild to moderate pain, fever, and inflammation. They work by reducing the levels of prostaglandins, which are chemicals that are responsible for pain and the fever and tenderness that occur with inflammation. Etodolac blocks the cyclooxygenase (abbrev. COX) enzymes which form prostanoids, resulting in lower concentrations of prostaglandins. Consequently, inflammation, pain and fever are reduced.
Accordingly, there is a need to industrially acceptable /scalable process 2-ethyl phenyl hydrazine hydrochloride and 7-Ethyl tryptophol in high yields compared to prior-art processes.
The inventors of the present invention have developed economical and commercially scalable process for the synthesis of 2-ethyl phenyl hydrazine hydrochloride, starting from commercially available 2-ethylaniline. Diazotisation of 2-Ethyl aniline by using HCl and sodium nitrite followed by reduction with sodium sulphite in the presence of Conc. Hydrochloric acid with high yielding 2-ethyl phenyl hydrazine hydrochloride. Specifically maintaining controlled low temperature with the use of dry ice, liquid nitrogen (internally). The process is operationally very easy, inexpensive, and high yielding to get pure solid.
Further, the process of the present invention involves use of water immiscible solvent due to which recovery is high and hence industrially and economically feasible process and has safe operations.

OBJECTIVE OF THE INVENTION
The main objective of the present invention is to provide an improved process for the preparation of a Tryptophol intermediate.
Another objective of the present invention is to provide an improved process for the preparation of 7- Ethyl Tryptophol having the Formula (Ia)
Formula (Ia)
Yet another objective of the present invention is to provide an improved process for the preparation of - Ethyl Tryptophol having the Formula (Ia).
Formula (Ia)
which is commercially feasible / industrially scalable which involves use of simple and commercially available starting materials.
Still another objective of the present invention is to provide process for the preparation of 2-ethylphenyl hydrazine having the Formula (IIa)
Formula (IIa)

or its salts useful in the preparation of compound of Formula (Ia).

SUMMARY OF THE INVENTION
Accordingly, the present invention provides an improved process for the preparation of a Tryptophol intermediate of the formula (I)
Formula (I)
where R represents, alkyl, aryl, aralkyl, substituted alkyl, hydroxyl, alkoxy, halogen group.

The present invention specifically provides an improved process for the preparation of - Ethyl Tryptophol having the Formula (Ia)
Formula (Ia)

The present invention provides an improved process for the preparation of 7- Ethyl Tryptophol having the Formula (I)
Formula (I)
or its salts, which comprises :
(a). diazotizing a compound of Formula (III)
Formula (III)
using a diazotizing agent in a solvent to obtain a compound of Formula (IV),
Formula (IV)
(b). converting compound of Formula (IV) using sodium sulfite, an acid, in a solvent to obtain a compound of Formula (II),
Formula (II)

or its salts,
(c). reacting compound of formula (II) with 2,3-dihydrofuran in a water immiscible solvent optionally using a catalyst to obtain compound of Formula (I).
The present invention provides an improved process for the preparation of 7- Ethyl Tryptophol having the Formula (Ia)
Formula (Ia)

or its salts, which comprises :
(a). diazotizing a compound of Formula (IIIa)
Formula (IIIa)
using a diazotizing agent in a solvent to obtain a compound of Formula (IVa),
Formula (IVa)
(b). converting compound of Formula (IVa) using sodium sulfite, an acid, in a solvent to obtain a compound of Formula (IIa),
Formula (IIa)
or its salts,
(c). reacting compound of formula (IIa) with 2,3-dihydrofuran in a water immiscible solvent optionally using a catalyst to obtain compound of Formula (Ia).
The present invention relates to an improved process for the preparation of 2-ethylphenyl hydrazine having the Formula (IIa)
Formula (IIa)

or its salts, which comprises :
(a). diazotizing a compound of Formula (IIIa)
Formula (IIIa)
using a diazotizing agent, in a solvent to obtain a compound of Formula (IVa),
Formula (IVa)

(b). converting compound of Formula (IVa) using sodium sulfite, an acid, in a solvent to obtain a compound of Formula (IIa), or its salts.

DETAILED DESCRIPTION OF THE INVENTION
The term "comprising", which is synonymous with "including", "containing", or "characterized by" here is defined as being inclusive or open-ended, and does not exclude additional, unrecited elements or method steps, unless the context clearly requires otherwise.
The term alkyl as used herein represents methyl, ethyl, propyl, isopropyl, butyl etc.
The term aryl as used herein represents phenyl, napthyl etc.
The term aralkyl as used herein represents benzyl, phenethyl, etc.
The term substituted alkyl as used herein represents hydroxyalkyl, alkoxyalkyl, sulfonylalkyl etc.
The diazotizing agent used in this reaction include but not limited to Sodium nitrite and the mineral acid, preferably HCl.
The acid as used in the reaction medium is one or more selected from hydrochloric acid, hydrobromic acid, Sulphuric acid, phosphoric acid, acetic acid, p-toluene sulfonic acid, Citric acid, Tartaric acid, formic acid or mixture thereof.
The catalyst as used in the reaction medium is one or more selected from Tetra butyl ammonium bromide, Tetra butyl ammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium sulfate etc.
The solvent system used in the reaction medium is water, one or more aromatic hydrocarbon solvents selected from toluene, xylene, cyclohexane, styrene, diethylbenzene, ethylbenzene; phenols, ethers such as diethyl ether, disoproyl ether, Methyl tert-Butyl Ether, 2-methylTHF.

The reaction of 1-(2-ethylphenyl) hydrazine hydrochloride with 2,3-dihydrofuran is carried out at a temperature of 25 to 120ºC. The diazotization reaction was carried out at a temperature of 0 to 100ºC.
The temperature during diazotization reaction can be maintained by using Dry ice, Liquid Nitrogen to control the exothermic reaction and also to avoid decomposition of highly unstable diazonium chloride.
The novelty of the invention lies in the use of dry ice, Liquid Nitrogen during the manufacturing the 2-ethylphenyl hydrazine hydrochloride for maintaining/ controlling required low temperatures during the exothermic reaction process. Another novelty of the process is use of water immiscible solvents in the reaction of 2-ethylphenyl hydrazine hydrochloride with 2,3-dihydrofuran. Another important feature of the present invention is use of lesser quantities of 2,3-dihydrofuran which minimizes formation adduct impurity of the structure

The intermediates formed in the present invention may be isolated or not. Any of the above reactions may be carried out in-situ reactions. The above compounds may be isolated as salts or free bases, if the above compounds are isolated as salts they are converted to their free bases first and used for further reactions.
The present invention is further illustrated by the following examples which are provided merely to be exemplary of the inventions and is not intended to limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

EXAMPLES
Example- 1: Preparation of 2-ethylphenyl hydrazine hydrochloride:
To a pre-cooled (below 0°C; using crushed ice and salt mixture) dilute Hydrochloric acid [Conc. Hydrochloric acid (216 ml) and process water (100 ml)] in a 3 neck round bottomed flask, charge drop-wise 2-ethyl aniline (pre-cooled to 0°C; 100 g) in over a period of 1 hr at below 0°C and stir for 25 – 35 mins at below 0°C. Charge slowly freshly prepared pre-cooled to 0°C solution of Sodium nitrite [Dissolve Sodium nitrite (60 g) in process water (124 ml)] over a period of 55 – 65 min at below 0°C. Maintain the reaction mass for 20 - 30 mins at below 0°C.
Charge the above diazonium salt solution to another 3 neck round bottomed flask containing suspension of Sodium sulfite (416 g) in process water (600 ml) and Conc. Hydrochloric acid (100 ml) at below 5°C and stir the reaction mass for 1 hr.
Gradually heat the reaction mass up to 80- 85°C under stirring and stir at 80- 85°C for 7- 8 hr. Note: Scrubber to be connected. Cool the reaction mass to 30- 35°C and stir for 20- 30 mins at 30- 35°C and charge Conc Hydrochloric acid (620 ml) at the same temperature. Cool the reaction mass to room temperature and stir for 1- 2 hr at about 20 - 25°C. (Note: Material formation will be observed). Filter the solids, wash the wet solid with filtered MLs (100 ml). Note: Scrubber to be connected. Suck dry for 50 – 60 min and unload and charge to another 3 neck round bottomed flask containing Process water (600 ml), heat to 85 to 90°C and stir for 1 hr. Cool the reaction mass to 25 to 30°C and add conc. Hydrochloric acid (100 ml) under stirring and cool the reaction mass to 0 to 5°C and stir for 2 hrs. Filter the solid and wash the wet solid with filtered MLs (100 ml). Suck dry for 50 – 60 min and unload the wet solid (140 g) and dry at 55 – 60°C for 10 – 12 hr to get dry 2-ethylphenyl hydrazine hydrochloride solid (120 g; 84.1%).
Purity:99.11%; Assay 99.0%.

Example- 2: Preparation of 2-ethylphenyl hydrazine hydrochloride:
To a pre-cooled (below 0°C; using dry ice to the reaction mass/ With compressor) dilute Hydrochloric acid [Conc. Hydrochloric acid (216 ml) and Process water (100 ml)] in a 3 neck round bottomed flask, charge drop-wise 2-ethyl aniline (pre-cooled to 0°C; 100 g) in over a period of 1 hr at below 0°C and stir for 25 – 35 mins at below 0°C. Charge slowly freshly prepared pre-cooled to 0°C solution of Sodium nitrite [Dissolve Sodium nitrite (60 g) in process water lot- 2 (124 ml)] over a period of 55 – 65 min at below 0°C. Maintain the reaction mass for 20 - 30 mins at below 0°C.
Charge the above diazonium salt solution to another 3 neck round bottomed flask containing suspension of Sodium sulfite (416 g) in process water (600 ml) at room temperature and stir the reaction mass for 1 hr.
Gradually heat the reaction mass up to 50- 60°C under stirring and charge slowly conc. Hydrochloric acid lot- 2 (103 ml) under stirring at 50- 60°C. Note: Scrubber to be connected. Raise the temperature to 80°C and stir at 80- 85°C for 7- 8 hr.
Cool the reaction mass to 30- 35°C and stir for 20- 30 mins at 30- 35°C and charge Conc Hydrochloric acid (620 ml) at the same temperature.
Cool the reaction mass to room temperature and stir for 1- 2 hr at about 20 - 25°C. (Note: Material formation will be observed). Filter the solids, wash the wet solid with filtered MLs (100 ml). Note: Scrubber to be connected. Suck dry for 50 – 60 min and unload the wet solid (130 - 150 g) and dry at 55 – 60°C for 10 – 12 hr to get Dry 2-ethylphenyl hydrazine hydrochloride (120 g; 84.1%).
Purity:_99+%_; Assay _98+%_%.

Example- 3: Preparation of 2-ethylphenyl hydrazine hydrochloride:
To a pre-cooled (below 0°C; using crushed ice and salt mixture) dilute Hydrochloric acid [Conc. Hydrochloric acid (2.16 Lit) and Process water (1.0 Lit)] in a 3 neck round bottomed flask, charge drop-wise 2-ethyl aniline (pre-cooled to 0°C; 1.0 Kg) in over a period of 1 hr at below 0°C and stir for 25 – 35 mins at below 0°C. Charge slowly freshly prepared pre-cooled to 0°C solution of Sodium nitrite [Dissolve Sodium nitrite (0.60 Kg) in process water (1.24 Lit)] over a period of 2 hr at below 0°C. Maintain the reaction mass for 20 - 30 mins at below 0°C.
Charge the above diazonium salt solution to another 3 neck round bottomed flask containing suspension of Sodium sulfite (4.16 Kg) in process water (6.0 Lit) and Conc. Hydrochloric acid (1.0 Lit) at below 5°C and stir the reaction mass for 1 hr.
Gradually heat the reaction mass up to 80- 85°C under stirring and stir at 80- 85°C for 7- 8 hr. Note: Scrubber to be connected. Cool the reaction mass to 30- 35°C and stir for 20- 30 mins at 30- 35°C and charge Conc Hydrochloric acid (6.2 Lit) at the same temperature. Cool the reaction mass to room temperature and stir for 1- 2 hr at about 20 - 25°C. (Note: Material formation will be observed). Filter the solids, wash the wet solid with filtered MLs (1.0 Lit). Note: Scrubber to be connected. Suck dry for 50 – 60 min and unload and charge to another 3 neck round bottomed flask containing Process water (6.0 Lit), heat to 85 to 90°C and stir for 1 hr. Cool the reaction mass to 25 to 30°C and add conc. Hydrochloric acid (1.0 Lit) under stirring and cool the reaction mass to 0 to 5°C and stir for 2 hrs. Filter the solid and wash the wet solid with filtered MLs (1.0 Lit). Suck dry for 50 – 60 min and unload the wet solid (1.45 Kg) and dry at 55 – 60°C for 10 – 12 hr to get dry 2-ethylphenyl hydrazine hydrochloride solid (1.20 Kg; 84.1%).
Purity:99.95%; Assay 99.6%.

Example- 4: Preparation of 2-ethylphenyl hydrazine hydrochloride:
To a pre-cooled (below 0°C; using plant compressor) dilute Hydrochloric acid [Conc. Hydrochloric acid (108 Lit) and Process water (50 Lit)] in a 3 neck round bottomed flask, charge drop-wise 2-ethyl aniline (pre-cooled to 0°C; 50 Kg) in over a period of 1 hr at below 0°C and stir for 25 – 35 mins at below 0°C. Charge slowly freshly prepared pre-cooled to 0°C solution of Sodium nitrite [Dissolve Sodium nitrite (30 Kg) in process water (62 Lit)] over a period of 16 hr at below 5°C. Maintain the reaction mass for 20 - 30 mins at below 5°C. (Note: Controlling the exothermicity using Compressor to maintain below 0°C was not possible in a given 2 hr time).
Charge the above diazonium salt solution to another 3 neck round bottomed flask containing suspension of Sodium sulfite (208 Kg) in process water (300 Lit) and Conc. Hydrochloric acid (50 Lit) at below 5°C and stir the reaction mass for 1 hr.
Gradually heat the reaction mass up to 80- 85°C under stirring and stir at 80- 85°C for 7- 8 hr. Note: Scrubber to be connected. Cool the reaction mass to 30- 35°C and stir for 20- 30 mins at 30- 35°C and charge Conc Hydrochloric acid (310 Lit) at the same temperature. Cool the reaction mass to room temperature and stir for 1- 2 hr at about 20 - 25°C. (Note: Material formation will be observed). Filter the solids, wash the wet solid with filtered MLs (50 Lit). Note: Scrubber to be connected. Suck dry for 50 – 60 min and unload and charge to another 3 neck round bottomed flask containing Process water (300 Lit), heat to 85 to 90°C and stir for 1 hr. Cool the reaction mass to 25 to 30°C and add conc. Hydrochloric acid (50 Lit) under stirring and cool the reaction mass to 0 to 5°C and stir for 2 hrs. Filter the solid and wash the wet solid with filtered MLs (50 Lit). Suck dry for 50 – 60 min and unload the wet solid (45 Kg) and dry at 55 – 60°C for 10 – 12 hr to get dry 2-ethylphenyl hydrazine hydrochloride solid (18 Kg; 25.26%).
Purity:99.9, Assay:99.1%

Example- 5: Preparation of 2-ethylphenyl hydrazine hydrochloride:
To a pre-cooled (below 0°C; using dry ice addition to the reaction mass) dilute Hydrochloric acid [Conc. Hydrochloric acid (216 ml) and Process water (100 ml)] in a 3 neck round bottomed flask, charge drop-wise 2-ethyl aniline (pre-cooled to 0°C; 100 g) in over a period of 1 hr at below 0°C and stir for 25 – 35 mins at below 0°C. Charge slowly freshly prepared pre-cooled to 0°C solution of Sodium nitrite [Dissolve Sodium nitrite (60 g) in process water (124 ml)] over a period of 30 min at below 0°C. Maintain the reaction mass for 20 - 30 mins at below 0°C.
Charge the above diazonium salt solution to another 3 neck round bottomed flask containing suspension of Sodium sulfite (416 g) in process water (600 ml) at room temperature and stir the reaction mass for 1 hr.
Gradually heat the reaction mass up to 50- 60°C under stirring and charge slowly conc. Hydrochloric acid lot- 2 (103 ml) under stirring at 50- 60°C. Raise the temperature to 80°C and stir at 80- 85°C for 7- 8 hr. Note: Scrubber to be connected. Cool the reaction mass to 30- 35°C and stir for 20- 30 mins at 30- 35°C and charge Conc Hydrochloric acid (620 ml) at the same temperature. Cool the reaction mass to room temperature and stir for 1- 2 hr at about 20 - 25°C. (Note: Material formation will be observed). Filter the solids, wash the wet solid with filtered MLs (100 ml). Note: Scrubber to be connected. Suck dry for 50 – 60 min and unload and charge to another 3 neck round bottomed flask containing Process water (600 ml), heat to 85 to 90°C and stir for 1 hr. Cool the reaction mass to 25 to 30°C and add conc. Hydrochloric acid (100 ml) under stirring and cool the reaction mass to 0 to 5°C and stir for 2 hrs. Filter the solid and wash the wet solid with filtered MLs (100 ml). Suck dry for 50 – 60 min and unload the wet solid (140 g) and dry at 55 – 60°C for 10 – 12 hr to get dry 2-ethylphenyl hydrazine hydrochloride solid (120 g; 84.1%).
Purity:99.12, Assay:98.7%

Example- 6: Preparation of 2-ethylphenyl hydrazine hydrochloride:
To a pre-cooled (below 0°C; using Dry ice addition to the reaction mass) dilute Hydrochloric acid [Conc. Hydrochloric acid (432 Lit) and Process water (200 Lit)] in a 3 neck round bottomed flask, charge drop-wise 2-ethyl aniline (pre-cooled to 0°C; 200 Kg) in over a period of 1 hr at below 0°C and stir for 25 – 35 mins at below 0°C. Charge slowly freshly prepared pre-cooled to 0°C solution of Sodium nitrite [Dissolve Sodium nitrite (120 Kg) in process water (248 Lit)] over a period of 1.5 hr at below 0°C. Maintain the reaction mass for 20 - 30 mins at below 0°C.
Charge the above diazonium salt solution to another 3 neck round bottomed flask containing suspension of Sodium sulfite (832 Kg) in process water (1200 Lit) and Conc. Hydrochloric acid (200 Lit) at below 5°C and stir the reaction mass for 1 hr.
Gradually heat the reaction mass up to 50- 60°C under stirring and charge slowly conc. Hydrochloric acid (206 Lit) under stirring at 50- 60°C. Raise the temperature to 80°C and stir at 80- 85°C for 7- 8 hr. Note: Scrubber to be connected. Cool the reaction mass to 30- 35°C and stir for 20- 30 mins at 30- 35°C and charge Conc Hydrochloric acid (1240 Lt) at the same temperature. Cool the reaction mass to room temperature and stir for 1- 2 hr at about 20 - 25°C. (Note: Material formation will be observed). Filter the solids, wash the wet solid with filtered MLs (200 Lit). Note: Scrubber to be connected. Suck dry for 50 – 60 min and unload and charge to another 3 neck round bottomed flask containing Process water (1200 Lit), heat to 85 to 90°C and stir for 1 hr. Cool the reaction mass to 25 to 30°C and add conc. Hydrochloric acid (200 Lit) under stirring and cool the reaction mass to 0 to 5°C and stir for 2 hrs. Filter the solid and wash the wet solid with filtered MLs (200 Lit). Suck dry for 50 – 60 min and unload the wet solid (304 Kg) and dry at 55 – 60°C for 10 – 12 hr to get dry 2-ethylphenyl hydrazine hydrochloride solid (240 Kg; 81.4%).
Purity:99.0, Assay:98.8%

Example- 7: Preparation of 7- Ethyl tryptophol crude.
Charge drop-wise a solution of 2,3-dihydrofuran (105 g) in Toluene (3000 ml) to a mixture of process water (3000 ml), 1-(2-ethylphenyl) hydrazine hydrochloride (300 g), Sulphuric acid (15 g) and Tetra butyl ammonium bromide (15 g) in a 3 neck round bottomed flask at 70- 75°C under vigorous stirring over a period of 40 - 50 min. (Note: Reaction is Exothermic; temperature should be maintained at 70 to 75 °C, high RPM should be maintained).
Slowly heat the reaction mass to 85- 90°C under stirring and stir for about 3 hr. Monitor the reaction by TLC/ HPLC. After completion of the reaction, Allow the reaction mass to cool to room temperature. Separate the organic layer and aqueous layer. Extract the aqueous layer with Toluene (900 ml) at room temperature. Combine the organic layers and wash with 7% Sodium bicarbonate solution (300 ml) and concentrate the organic layer under vacuum at 60 to 70°C to give the crude compound. Unload the product (255 g; 77.27%) and submit for analysis.
Purity is 80.22% and Assay is 46.97%.

Example- 8: Preparation of 7- Ethyl tryptophol crude.
Charge drop-wise a solution of 2,3-dihydrofuran (7 g) in o-Xylene (200 ml) to a mixture of process water (200 ml), 1-(2-ethylphenyl) hydrazine hydrochloride (20 g), Sulphuric acid (2 g) in a 3 neck round bottomed flask at 90- 95°C under vigorous stirring over a period of 40 - 50 min. (Note: Reaction is Exothermic; temperature should be maintained at 90 to 95 °C, high RPM should be maintained).
Slowly heat the reaction mass to 105- 110°C under stirring and stir for about 1 hr. Monitor the reaction by TLC/ HPLC. After completion of the reaction, Allow the reaction mass to cool to room temperature. Separate the organic layer and aqueous layer. Extract the aqueous layer with o-Xylene (60 ml) at room temperature. Combine the organic layers and wash with 7% Sodium bicarbonate solution (20 ml) and concentrate the organic layer under vacuum at 70 to 80°C to give the crude compound. Unload the product 15 g; 68.18%) and submit for analysis.
Purity is 83.45% and assay is 58.78%.

Example- 9: Preparation of 7- Ethyl tryptophol crude.
Charge drop-wise a solution of 2,3-dihydrofuran (40 g) in Methyl tert- Butyl Ether (500 ml) to a mixture of process water (500 ml), 1-(2-ethylphenyl) hydrazine hydrochloride (100 g), Sulphuric acid (10 g) and Methyl tert- Butyl Ether (500 ml) in a 3 neck round bottomed flask at 50- 55°C under vigorous stirring over a period of 50 - 60 min. (Note: Reaction is slightly Exothermic; temperature should be maintained at 50 to 60°C and stir for about 1 hr. Monitor the reaction by TLC/ HPLC. After completion of the reaction, Allow the reaction mass to cool to room temperature. Separate the organic layer and aqueous layer. Extract the aqueous layer with Methyl tert- Butyl Ether (300 ml) at room temperature. Combine the organic layers and wash with 1 N Hydrochloric acid (300 X 2) and with 7% Sodium bicarbonate solution (300 ml X 2) and concentrate the organic layer under vacuum at below 50°C to give the crude compound. Unload the product (76 g; 69.09%) and submit for analysis.
Purity is 75.5% and assay is 54.7%.

Example- 10: Preparation of 7- Ethyl tryptophol crude (without TBABr).
Charge drop-wise a solution of 2,3-dihydrofuran (52.5 g) in Toluene (1500 ml) to a mixture of process water (1500 ml), 1-(2-ethylphenyl) hydrazine hydrochloride (150 g), Sulphuric acid (7.5 g) in a 3 neck round bottomed flask at 70- 75°C under vigorous stirring over a period of 40 - 50 min. (Note: Reaction is Exothermic; temperature should be maintained at 70 to 75 °C, high RPM should be maintained).
Slowly heat the reaction mass to 85- 90°C under stirring and stir for about 3 hr. Monitor the reaction by TLC/ HPLC. After completion of the reaction, Allow the reaction mass to cool to room temperature. Separate the organic layer and aqueous layer. Extract the aqueous layer with Toluene (450 ml) at room temperature. Note: During organic layer separation Gummy residues was observed.
Combine the organic layers and wash with 7% Sodium bicarbonate solution (300 ml) and concentrate the organic layer under vacuum at below 60°C to give the crude compound. Unload the product (130 g; 78.79%) and submit for analysis.
Purity is 84.94% and Assay is 47.01%.

Example- 11: Preparation of 7- Ethyl tryptophol crude. (With TBABr).
Charge drop-wise a solution of 2,3-dihydrofuran (52.5 g) in Toluene (1500 ml) to a mixture of process water (1500 ml), 1-(2-ethylphenyl) hydrazine hydrochloride (150 g), Sulphuric acid (7.5 g) and Tetra butyl ammonium bromide (7.5 g) in a 3 neck round bottomed flask at 70- 75°C under vigorous stirring over a period of 40 - 50 min. (Note: Reaction is Exothermic; temperature should be maintained at 70 to 75 °C, high RPM should be maintained).
Slowly heat the reaction mass to 85- 90°C under stirring and stir for about 3 hr. Monitor the reaction by TLC/ HPLC. After completion of the reaction, allow the reaction mass to cool to room temperature. Separate the organic layer and aqueous layer. Extract the aqueous layer with Toluene (450 ml) at room temperature. Note: During organic layer separation Gummy residues was not observed.
Combine the organic layers and wash with 7% Sodium bicarbonate solution (300 ml) and concentrate the organic layer under vacuum at 60 to 70°C to give the crude compound. Unload the product (127 g; 77.27%) and submit for analysis.
Purity is 80.72% and Assay is 48.56%.

Example- 12: Preparation of 7- Ethyl tryptophol crude.
Charge drop-wise a solution of 2,3-dihydrofuran (8.75 g) in Toluene (250 ml) to a mixture of process water (25 ml), 1-(2-ethylphenyl) hydrazine hydrochloride (25 g), Tartaric acid (1.25 g) in a 3 neck round bottomed flask at 70- 75°C under vigorous stirring over a period of 40 - 50 min. (Note: Reaction is Exothermic; temperature should be maintained at 70 to 75 °C, high RPM should be maintained).
Slowly heat the reaction mass to 85- 90°C under stirring and stir for about 3 hr. Monitor the reaction by TLC/ HPLC. After completion of the reaction, Allow the reaction mass to cool to room temperature. Separate the organic layer and aqueous layer. Extract the aqueous layer with Toluene (125 ml) at room temperature. Combine the organic layers and concentrate the organic layer under vacuum at 60 to 70°C to give the crude compound. Unload the product (20 g).

Example- 13: Preparation of 7- Ethyl tryptophol crude.
Charge drop-wise a solution of 2,3-dihydrofuran (8.75 g) in Toluene (250 ml) to a mixture of process water (250 ml), 1-(2-ethylphenyl) hydrazine hydrochloride (25 g), Phosphoric acid (1.25 g) and Tetra butyl ammonium bromide (1.25 g) in a 3 neck round bottomed flask at 70- 75°C under vigorous stirring over a period of 40 - 50 min. Slowly heat the reaction mass to 85- 90°C under stirring and stir for about 3 hr. After isolation as per the procedure gave product (24 g).

Example- 14: Preparation of 7- Ethyl tryptophol crude.
Charge drop-wise a solution of 2,3-dihydrofuran (8.75 g) in Toluene (125 ml) to a mixture of process water (125 ml), 1-(2-ethylphenyl) hydrazine hydrochloride (25 g), para Toluene Sulfonic Acid (2.5 g) in a 3 neck round bottomed flask at 70- 75°C under vigorous stirring over a period of 40 - 50 min. Slowly heat the reaction mass to 85- 90°C under stirring and stir for about 3 hr. After isolation as per the procedure gave product (15 g).

Example- 15: Preparation of 7- Ethyl tryptophol crude. (HCl as Catalyst).
Charge drop-wise a solution of 2,3-dihydrofuran (8.75 g) in Toluene (250 ml) to a mixture of process water (250 ml), 1-(2-ethylphenyl) hydrazine hydrochloride (25 g) in a 3 neck round bottomed flask at 70- 75°C under vigorous stirring over a period of 40 - 50 min. (Note: Reaction is Exothermic; temperature should be maintained at 70 to 75 °C, high RPM should be maintained).
Slowly heat the reaction mass to 85- 90°C under stirring and stir for about 3 hr. Monitor the reaction by TLC/ HPLC. After isolation as per the procedure gave product (23 g).

Example- 16: Preparation of 7- Ethyl tryptophol crude from 2-ethyl aniline.
To a pre-cooled (below 0°C; using dry ice to the reaction mass/ With compressor) dilute Hydrochloric acid [Conc. Hydrochloric acid (500 ml) and Process water (184 ml)] in a 3 neck round bottomed flask, charge drop-wise 2-ethyl aniline (pre-cooled to 0°C; 100 g) in over a period of 1 hr at below 0°C and stir for 25 – 35 mins at below 0°C. Charge slowly freshly prepared pre-cooled to 0°C solution of Sodium nitrite [Dissolve Sodium nitrite (125 g) in process water lot- 2 (176 ml)] over a period of 55 – 65 min at below 0°C. Maintain the reaction mass for 20 - 30 mins at below 0°C.
Charge the above diazonium salt solution to another 3 neck round bottomed flask containing suspension of Sodium sulfite (832 g) in process water (1560 ml) at room temperature and stir the reaction mass for 1 hr.
Gradually heat the reaction mass up to 80- 85°C under stirring, stir for 2 hr and charge slowly conc. Hydrochloric acid lot- 2 (800 ml) under stirring at 80- 85°C. Note: Scrubber to be connected. Stir at 80- 85°C for 4 hr.
Cool the reaction mass to 30- 35°C and stir for 60 mins at 30- 35°C and charge Toluene (800 ml) at room temperature.
Slowly adjust the reaction mass pH 7.5 - 8.5 with aqueous ammonia (560 ml) at 25±5°C. Separate the organic layer.
Separately prepare a mixture of Sulfuric acid (68 g) in process water (1800 ml), Toluene (1000 ml) and cool the reaction mass to 10°C and charge into organic layer at below 10°C.
Prepare 2,3 Dihydrofuran (92.56 g) aqueous solution in process water (200 ml) in another flask in presence of Hydrochloric acid (2 ml) at room temperature and charge to the organic layer containing dilute sulfuric acid under stirring at 5°C. Stir the reaction mass for 60 min and raise the temperature to 70°C and charge slowly Sulfuric acid (68 g) over a period of 30 min. Stir the mass for 3 hr at 75 to 80°C. Monitor the reaction by TLC / HPLC.
After completion of reaction cool to 60°C and separate the organic layer concentrate to get 240 g of 7- Ethyl tryptophol crude

Example- 17: Distillation of 7- Ethyl tryptophol crude to get Technical.

7- Ethyl Tryptophol Crude (250 g) was heated in a 2 neck round bottomed flask equipped with distillation condenser and high vacuum pump with 0.3 mmHg pressure to 140 - 170°C under vacuum and collected the fraction 1 completely under vacuum at 1 mmHg.
Then temperature of the reaction mass was raised to 200 - 250°C under stirring and collected the fraction 2 separately at 180 - 200°C vapor pressure at 1 mmHg using warm water (40 – 45°C) condenser. Unload Fraction- 2 (Step- 2 yield is 93 g; 37.25%).
Purity is 83.63% and Assay is 87.0%.

Example- 18: Distillation of 7- Ethyl tryptophol crude to get Technical.

7- Ethyl Tryptophol Crude (250 g) was heated in a 2 neck round bottomed flask equipped with distillation condenser and high vacuum pump with 0.3 mmHg pressure to 140 - 170°C under vacuum and collected the fraction 1 completely under vacuum at 1 mmHg.
Then temperature of the reaction mass was raised to 200 - 220°C under stirring and collected the fraction 2 separately at 180 - 190°C vapor pressure at 1 mmHg using warm water (40 – 45°C) condenser. Unload Fraction- 2 (Step- 2; 150 g; 60%).
Purity is 94.16% and Assay is 91.55%.

Example- 19: Distillation of 7- Ethyl tryptophol crude to get Technical.
Heat the 7- Ethyl Tryptophol Crude (227 g) in a 2 neck round bottomed flask equipped with distillation condenser and high vacuum pump with 0.3 mmHg pressure to 70 - 130°C under vacuum and collect the fraction 1 completely under vacuum at 1 mmHg.
Then raise the reaction mass temperature to 200 - 220°C under stirring and collect the fraction 2 separately at 140 - 180°C vapor pressure at 1 mmHg using warm water (40 – 45°C) condenser. Unload Fraction- 2 and send the Fraction-I and Fraction-II (Step- 2; 139 g; 61.23%)

Purity is 92.60% and Assay is _83.78%.

Example- 20: Distillation of 7- Ethyl tryptophol crude to get Technical.
7- Ethyl Tryptophol Crude (232 g) was heated in a 2 neck round bottomed flask equipped with distillation condenser and high vacuum pump with 0.3 mmHg pressure to 80 to 130°C under vacuum and collect the fraction 1 completely under vacuum at 0.3 mmHg.
Then temperature of the reaction mass was raised to 200 - 210°C under stirring and collect the fraction 2 separately at 130 - 190°C vapor pressure at 0.3 mmHg using warm water (40 – 45°C) condenser. Unload Fraction- 2 (Step- 2; 135 g).
Purity is 88.76% and Assay is 71.31%.

Example- 21: Preparation of 7-ethyl tryptophol Pure:
7- Ethyl Tryptophol Technical (100 g) was crystallized from a mixture of Toluene (200 ml) and Cyclohexane (200 ml), followed by filtration and washing with Cyclohexane (200 ml) to get pure 7- Ethyl Tryptophol (70 g; 70%).
Purity is 99.46% and Assay is 99.14%.

Example- 22: Preparation of 7-ethyl tryptophol Pure:
7-Ethyl tryptophol (100 g) was dissolved in Toluene (200 ml) and stir for 15 to 20 min at room temperature, Cyclohexane (200 ml) was added to the reaction mass at room temperature and stir the reaction mass for 15 to 20 min. The reaction mass was cooled to -2 to 2 °C. and maintained it for 1 to 2 h. Filter the reaction mass and wash with 50 ml of chilled Solvent mixture (Toluene and Cyclohexane; 1:1) and suck dry for 15 to 20 min, unload the wet material, and dry it to get solid product (65 g).
Purity:99.23%; Assay:98.61%

Example- 23: Preparation of 7-ethyl tryptophol Pure:

7-Ethyl tryptophol (100 g) was dissolved in Toluene (150 ml) and stir for 15 to 20 min at room temperature, Cyclohexane (100 ml) was added to the reaction mass at room temperature and stir the reaction mass for 15 to 20 min. The reaction mass was cooled to -2 to 2 °C. and maintained it for 1 to 2 h. Filter the reaction mass and wash with 50 ml of chilled Solvent mixture (Toluene and Cyclohexane; 1:1) and suck dry for 15 to 20 min, unload the wet material, and dry it to get solid product (66 g).
Purity:99.18%; Assay:98.81%

Example- 24: Preparation of 7-ethyl tryptophol Pure:
7-Ethyl tryptophol (100 g) was dissolved in Toluene (150 ml) and stir for 15 to 20 min at room temperature, Cyclohexane (150 ml) was added to the reaction mass at room temperature and stir the reaction mass for 15 to 20 min. The reaction mass was cooled to -2 to 2 °C. and maintained it for 1 to 2 h. Filter the reaction mass and wash with 50 ml of chilled Solvent mixture (Toluene and Cyclohexane; 1:1) and suck dry for 15 to 20 min, unload the wet material, and dry it to get solid product (68 g).
Purity:99.40%; Assay:98.97%

Example- 25: Preparation of 7-ethyl tryptophol Pure:
7-Ethyl tryptophol (100 g) was dissolved in Toluene (100 ml) and stir for 15 to 20 min at room temperature, Cyclohexane (200 ml) was added to the reaction mass at room temperature and stir the reaction mass for 15 to 20 min. The reaction mass was cooled to -2 to 2 °C. and maintained it for 1 to 2 h. Filter the reaction mass and wash with 50 ml of chilled Solvent mixture (Toluene and Cyclohexane; 1:1) and suck dry for 15 to 20 min, unload the wet material, and dry it to get solid product (65 g).
Purity:99.32%; Assay:97.1%

Example- 26: Preparation of 7-ethyl tryptophol Pure:
7-Ethyl tryptophol (100 g) was dissolved in Toluene (250 ml) and stir for 15 to 20 min at room temperature, Cyclohexane (50 ml) was added to the reaction mass at room temperature and stir the reaction mass for 15 to 20 min. The reaction mass was cooled to -2 to 2 °C. and maintained it for 1 to 2 h. Filter the reaction mass and wash with 50 ml of chilled Solvent mixture (Toluene and Cyclohexane; 1:1) and suck dry for 15 to 20 min, unload the wet material, and dry it to get solid product (60 g).
Purity:99.45%; Assay:98.39%

Example- 27: Preparation of 7-ethyl tryptophol Pure:
7-Ethyl tryptophol (100 g) was dissolved in Toluene (175 ml) and stir for 15 to 20 min at room temperature, Cyclohexane (125 ml) was added to the reaction mass at room temperature and stir the reaction mass for 15 to 20 min. The reaction mass was cooled to -2 to 2 °C. and maintained it for 1 to 2 h. Filter the reaction mass and wash with 50 ml of chilled Solvent mixture (Toluene and Cyclohexane; 1:1) and suck dry for 15 to 20 min, unload the wet material, and dry it to get solid product (64 g).
Purity:99.12%; Assay:98.62%.

Example- 28: Preparation of 7-ethyl tryptophol Pure:
7-Ethyl tryptophol Technical (100 g) was dissolved in Toluene (400 ml) and stir for 15 to 20 min at room temperature, The reaction mass was cooled to 10°C and seed (2 g) added under stirring to observe the crystallization. The reaction mass is further cooled to -10 to -15°C. and maintained it for 5 to 6 h at -15°C. Filter the reaction mass and wash with 100 ml of chilled Hexane (100 ml) and suck dry for 15 to 20 min, unload the wet material, and dry it to get solid product (67 g).
Purity : 99.85%; Assay:100.55%.
,CLAIMS:1. An improved process for the preparation of 7- Ethyl Tryptophol having the Formula (I)
Formula (I)
or its salts, which comprises :
(a). diazotizing a compound of Formula (III)
Formula (III)
using a diazotizing agent in a solvent to obtain a compound of Formula (IV),
Formula (IV)
(b). converting compound of Formula (IV) using sodium sulfite, an acid, in a solvent to obtain a compound of Formula (II),
Formula (II)

or its salts,
(c). reacting compound of formula (II) with 2,3-dihydrofuran in a water immiscible solvent optionally using a catalyst to obtain compound of Formula (I).

2. The process as claimed in claim 1 wherein the process for the preparation of 7- Ethyl Tryptophol having the Formula (Ia)
Formula (Ia)
or its salts, which comprises :
(a). diazotizing a compound of Formula (IIIa)
Formula (IIIa)
using a diazotizing agent in a solvent to obtain a compound of Formula (IVa),
Formula (IVa)
(b). converting compound of Formula (IVa) using sodium sulfite, an acid, in a solvent to obtain a compound of Formula (IIa),
Formula (IIa)
or its salts,
(c). reacting compound of formula (IIa) with 2,3-dihydrofuran in a water immiscible solvent optionally using a catalyst to obtain compound of Formula (Ia).

3. An improved process for the preparation of 2-ethylphenyl hydrazine having the Formula (IIa)
Formula (IIa)

or its salts, which comprises :
(a). diazotizing a compound of Formula (IIIa)
Formula (IIIa)
using a diazotizing agent, in a solvent to obtain a compound of Formula (IVa),
Formula (IVa)

(b). converting compound of Formula (IVa) using sodium sulfite, an acid, in a solvent to obtain a compound of Formula (IIa), or its salts.

4. The process as claimed in claims 1-3, wherein the diazotizing agent used in this reaction include but not limited to Sodium nitrite and the mineral acid.

5. The process as claimed in claims 1-4, wherein the acid is one or more selected from hydrochloric acid, hydrobromic acid, Sulphuric acid, phosphoric acid, acetic acid, p-toluene sulfonic acid, Citric acid, Tartaric acid, formic acid.

6. The process as claimed in claims 1-2, wherein the catalyst is one or more selected from Tetra butyl ammonium bromide, Tetra butyl ammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium sulfate.

7. The process as claimed in claims 1-3, wherein the solvent system used in the reaction medium is water, one or more aromatic hydrocarbon solvents selected from toluene, xylene, cyclohexane, styrene, diethylbenzene, ethylbenzene; phenols, ethers such as diethyl ether, disoproyl ether, Methyl tert-Butyl Ether, 2-methylTHF.

8. The process as claimed in claims 1- 2, wherein the reaction of compound of formula II or IIa with 2,3-dihydrofuran is carried out at a temperature of 25 to 120ºC.

9. The process as claimed in claims 1-3, wherein the diazotization reaction is carried out at a temperature of 0 to 100ºC.