DESC:FIELD
The present disclosure relates to a process for the synthesis of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
Various attempts have been made to prepare 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one which is used as an intermediate for Apixaban synthesis. Indian patent application no. 4558/CHE/2012 mentions the preparation of 3-chloro-1-(4-amino phenyl)-5,6-dihydropyridine-2-one by hydrogenating 3-chloro-1-(4-nitro phenyl)-5,6-dihydropyridine-2-one using Zn powder, HCl, IPA/dichloromethane as solvents a room temperature. Further, the Indian patent application no. 4558/CHE/2012 mentions the preparation of 3-chloro-1-(4-(2-oxopiperidine-1-yl)-phenyl)-5,6-dihydro pyridine-2-one by reacting 3-chloro-1-(4-(2-oxopiperidine-1-yl)-phenyl)-5,6-dihydro pyridine-2-one with bromopentanoyl chloride and potassium carbonate followed by reacting with NaH at 10-15 °C. Still further 4558/CHE/2012 suggests the preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydropyridine-2-oneby using (3-morpholino-1-(4-(2-nitrophenyl)-5,6-dihydropyridine-2(1h)-one); or by using (3-morpholino-1-(4-(2-aminophenyl)-5,6-dihydropyridine-2(1h)-one).
However, these and other processes for the preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one are complex, use expensive raw material, are time consuming, and are labour intensive. Further, the yield obtained for 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one using these conventional processes is not high and hence they are not commercially feasible.
Therefore, there is felt a need for a process for preparing 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one that mitigates the drawbacks mentioned hereinabove.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows.
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
An object of the present disclosure is to provide a process for the preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one.
Another object of the present disclosure is to provide a process for the preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one with comparatively higher yield and higher purity.
Still another object of the present disclosure is to provide a process for the preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one that is simple, rapid, economic and environment friendly.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.
SUMMARY
The present disclosure provides a process for preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one. The process comprises hydrogenating 3-chloro-1-(4-nitrophenyl)-5,6-dihydropyridine-2-one to obtain 3-chloro-1-(4-amino phenyl)-5,6-dihydropyridine-2-one.
In the second step, reacting 3-chloro-1-(4-amino phenyl)-5,6-dihydropyridine-2-one with 5-bromopentanoyl chloride obtain 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydropyridine-2-one.
In the third step, reacting 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one with morpholine to obtain 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one.
In step one, hydrogenation is carried out in alcohol selected from the group consisting of methanol, ethanol, propanol and butanol at a temperature in the range selected from 45 °C to 60 °C and under pressure selected from 5 to 10 kg/m2.
In one embodiment, the alcohol used in step (i) is methanol.
In step one, hydrogenation is carried out in in presence of Raney nickel catalyst in the range of 5wt% to 10 wt% of 3-chloro-1-(4-nitrophenyl)-5,6-dihydropyridine-2-one.
In step two, the reaction is carried out in a fluid medium selected from dichloromethane and dichloroethane, using at least one base selected from the group consisting of sodium carbonate, potassium carbonate, potassium hydroxide, sodium hydroxide, ammonium hydroxide and ammonium carbonate at a temperature in the range selected from 10 °C to 30 °C.
In one embodiment, the base used in step (ii) is a mixture of potassium carbonate and potassium hydroxide.
In one embodiment, the fluid medium used in step (ii) is dichloromethane.
In step three, the reaction is carried out in a fluid medium selected from the group consisting of chlorobenzene, toluene and benzene at a temperature in the range selected from 80 °C to 120 °C.
In one embodiment, the fluid medium used in step (iii) is chlorobenzene.

DETAILED DESCRIPTION
Embodiments, of the present disclosure, will now be described with reference to the accompanying drawing.
Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms "a,” "an," and "the" may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms "comprises," "comprising," “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure is not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.
The terms first, second, third, etc., should not be construed to limit the scope of the present disclosure as the aforementioned terms may be only used to distinguish one element, component, region, layer or section from another component, region, layer or section. Terms such as first, second, third etc., when used herein do not imply a specific sequence or order unless clearly suggested by the present disclosure.
3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one can be prepared from its intermediates. Conventional processes for the preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one are complex, use expensive raw material, are time consuming, are labour intensive and have a low yield; and hence are not commercially feasible.
Therefore, the present disclosure envisages a rapid, cost effective and simple process for the preparation of the 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one with comparatively higher yield and comparatively higher purity in comparison with the conventional processes.
In an aspect of the present disclosure, there is provided a process for preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one. In accordance with the present disclosure, the process for the preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one comprises the following steps:
i) Hydrogenating 3-chloro-1-(4-nitro phenyl)-5,6-dihydropyridine-2-one to obtain 3-chloro-1-(4-amino phenyl)-5,6-dihydropyridine-2-one;

ii) Reacting 3-chloro-1-(4-amino phenyl)-5,6-dihydropyridine-2-one with 5-bromopentanoyl chloride to obtain 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5, 6-dihydropyridine-2-one; and

iii) Reacting 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5, 6-dihydro pyridine-2-one with morpholine to obtain 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5, 6-dihydro pyridine-2-one.

The process is hereinafter described in detail.
Step I:
The scheme for the synthesis of 3-chloro-1-(4-amino phenyl)-5,6-dihydro pyridine-2-one in accordance with an embodiment of the present disclosure is given below:
In the first step, 3-chloro-1-(4-nitro phenyl)-5,6-dihydropyridine-2-one is dissolved in an alcohol to obtain a solution.
The alcohol can be selected from methanol, ethanol, propanol, and butanol.
In an exemplary embodiment, the alcohol is methanol.
The so obtained solution of 3-chloro-1-(4-nitro phenyl)-5,6-dihydropyridine-2-one is hydrogenated in the presence of Raney nickel catalyst at a temperature in the range of 45-60 oC, under a pressure ranging from 5-10 kg/cm2 to obtain a reaction mixture comprising 3-chloro-1-(4-amino phenyl)-5,6-dihydropyridine-2-one. The amount of Raney nickel catalyst used in the process can be in the range of 5 wt% to 10 wt%.
The reaction can be monitored by thin layer chromatography. The workup of the so obtained reaction mixture is carried out using known methods.
In an exemplary embodiment, the work up can be carried out by adding dichloromethane into the reaction mixture comprising 3-chloro-1-(4-amino phenyl)-5,6-dihydropyridine-2-one, under stirring and maintaining it for a period of 20-40 minutes to obtain a slurry. The so obtained slurry is filtered to obtain a residue (catalyst) and filtrate (3-chloro-1-(4-amino phenyl)-5,6-dihydropyridine-2-one).
The filtrate is distilled out at a temperature in the range of 60- 80 oC under stirring to obtain a reaction mass. The so obtained reaction mass is cooled to a temperature in the range of 0 oC to 5 oC and is maintained at the same temperature for 1 hour. The so obtained cooled reaction mass is then filtered to obtain a solid. The solid is washed with isopropyl alcohol and dried under vacuum at 50-70 oC for 4-10hrs to obtain 3-chloro-1-(4-amino phenyl)-5,6-dihydro pyridine-2-one having purity of at least 99% and a yield of at least 85%.
In the process of the present disclosure, 3-chloro-1-(4-amino phenyl)-5,6-dihydro pyridine-2-one is obtained with a yield in the range of 85% to 90% and purity in the range of 97.0% to 99.0%

Step II:
The scheme for the synthesis of 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5, 6-dihydropyridine-2-one, in accordance with an embodiment of the present disclosure is given below:

3-chloro-1-(4-amino phenyl)-5,6-dihydro pyridine-2-one obtained in Step-I is reacted with 5-bromopentanoyl chloride using at least one base and at least one fluid medium such as, dichloromethane, and dichloroethane to obtain 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydropyridine-2-one. In an exemplary embodiment, the fluid medium is dichloromethane.
In an embodiment, 3-chloro-1-(4–amino phenyl)-5,6-dihydropyridine-2-one obtained in the step I is dissolved in a fluid medium followed by adding at least one base in a reactor to obtain an admixture. The addition can be carried at a temperature in the range of 20 to 40 oC.
The base can be selected from the group consisting of sodium carbonate, potassium carbonate, potassium hydroxide, sodium hydroxide, ammonium hydroxide, ammonium carbonate, and the like. In an embodiment, the base is a mixture of 40% potassium carbonate solution and 50% potassium hydroxide solution.
The admixture can be cooled to a temperature in the range of 5 oC to 15 oC followed by slow addition of 5-bromopentanoyl chloride for 4-6 hours and maintaining the reaction at a temperature in the range of 20 to 40 oC for 4 to 6 hours to obtain a reaction mass. The reaction can be monitored by thin layer chromatography.
The so obtained reaction mass can be cooled to a temperature in the range of 10-15oC. TBAB (Tetrabutylammonium bromide) is added to the cooled reaction mass followed by the slow addition of 50% potassium hydroxide solution and maintaining the reaction mass for 3-4 hrs at 20-25oC to obtain a reaction mixture comprising 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydropyridine-2-one. The reaction can be monitored by thin layer chromatography.
The so obtained reaction mixture comprising 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one can be worked up using known techniques to obtain 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one having purity of at least 99 % and yield of at least 70%.
In the process of the present disclosure, 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one is obtained with a yield in the range of 70% to 75% and purity in the range of 97.0% to 99.0%
Step III:
The scheme for the synthesis of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5, 6-dihydro pyridine-2-one, in accordance with an embodiment of the present disclosure is given below:

3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydropyridine-2-one obtained in Step-II is reacted with morpholine to obtain 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one.
In one embodiment 3-chloro-1-(4-(2-oxopiperidine-1yl) phenyl)-5,6-dihydro pyridine-2-one obtained in the second step can be dissolved in a fluid medium, such as chlorobenzene, and toluene, at a temperature in the range of 25-30oC to obtain a mixture. The so obtained mixture is heated to a temperature in the range of 80-120 oC. Morpholine is added drop wise to the reaction mixture at a temperature in the range of 100-120 oC and maintained for 8 hours to 12 hours to obtain a reaction mass comprising 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydropyridine-2-one. In an exemplary embodiment, the fluid medium is chlorobenzene.

The so obtained reaction mass comprising 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydropyridine-2-one can be worked up using known techniques to obtain 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydropyridine-2-one having purity of at least 99 % and yield of at least 70%.

In the process of the present disclosure, 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydropyridine-2-one is obtained with a yield in the range of 70% to 75% and purity in the range of 97.0% to 99.0%

The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial scale.

EXPERIMENTAL DETAILS:
The foregoing description of the embodiments has been provided for purposes of illustration and not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
Experiment-1:
Step 1: Preparation of 3-chloro-1-(4-amino phenyl)-5,6-dihydro pyridine-2-one
1.0 Kg of 3-chloro-1-(4-nitro phenyl)-5,6-dihydropyridine-2-one was dissolved in 6 liters of methanol to obtain a solution. The so obtained solution was hydrogenated at 45oC in the presence of 70 gm Raney/Ni catalyst under 6 kg/cm2 pressures to obtain a reaction mixture. The reaction mixture was monitored by thin layer chromatography (TLC). After completion of the reaction dichloromethane (3.0 lit) was slowly added in the reaction mixture over 30 minutes and was further maintained for 30 min to obtain slurry. The slurry was filtered to separate the catalyst as a residue. The so obtained filtrate was distilled to obtain a mass. The so obtained mass was cooled to 0-5oC (chilled) and maintained for 1 hour. The so obtained chilled mass was then filtered to obtain a solid. The solid was washed with 200 ml of isopropyl alcohol (IPA) and dried under vacuum at 70oC for 8 hours to obtain 3-chloro-1-(4-amino phenyl)-5, 6-dihydro pyridine-2-one[Yield = 0.775 kg (88%); Purity (HPLC) = 99.0%].
Step 2: Preparation of 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one
6.0 lit dichloromethane was charged in a reactor at 30oC. 750 gm of 3–chloro-1-(4–amino phenyl)-5, 6-dihydro pyridine-2-one obtained in step 1 was charged at 30oC into the reactor under stirring. Further, 40% potassium carbonate solution (465 gm K2CO3 + 697.5 gm water) was charged into the reactor at 30oC under stirring to obtain the reaction mixture. The so obtained reaction mixture was cooled to 15oC followed by addition of 806.6gm of 5-bromopentanoyl chloride drop wise in 5 hours, at 15oC and was maintained for 5 hrs.at 25oC to obtain the reaction mass. The reaction was monitored by TLC (Thin layer chromatography). After completion of the reaction, the reaction mass was cooled to 15 oC.
45 gm of tetrabutyl ammonium bromide (TBAB) was added into the so obtained cooled reaction mass at 15 oC followed by addition of 250 ml of 50% potassium hydroxide solution (750 gm KOH +750 ml water) at 15 oC in 3 hrs and maintained it for 4 hrs at 25oC. The reaction was monitored by TLC.
After the completion of the reaction 3.2 liter water was added in the reaction mass and stirred for 30 minutes at 30oC followed by addition of 2.0 lit dichloromethane to obtain a biphasic mixture containing organic layer and aqueous layer. The organic layer was separated. The aqueous layer was further washed with 2 lit of dichloromethane. The organic layer was separated and the separated the organic layer was further washed with water 3.0 lit. The organic layer (dichloromethane) was distilled out at 50oC to obtain residue. 1.5 lit IPA was added in the so obtained residue and IPA was distilled out at 60oC under vacuum.
The residue was cooled to 5oC and maintained for 1hour. After one hour, the residue was filtered and washed with 100 ml IPA and dried under vacuum at 75oC for 6 hrs to obtain 3-chloro-1-(4-(2-oxopiperidine-1yl)phenyl)-5,6-dihydro pyridine-2-one having Yield = 0. 925 kg (74%); and Purity (HPLC) = 99.0%.
Step 3: Preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one
2.7 lit chlorobenzene and 900gm 3-chloro-1-(4-(2-oxopiperidine-1yl) phenyl)-5, 6-dihydro pyridine-2-oneobtained in step 2, were charged in the reactor/flask at 300C to obtain an admixture. The temperature of the admixture was raised to 110oC followed by drop wise addition of 772 gm morpholine in 5 hours and the reaction was maintained for 10 hours at 110oC to obtain a reaction mass. The reaction was monitored by TLC. After completion of reaction, the so obtained reaction mass was cooled to 80oC. 1.8 lit of water was added in the reaction mass in 20 min at 70 oC. After the addition of water the aqueous reaction mass was cooled to 5oC and maintained for 2 hours at the same temperature, to obtain a residue. The so obtained residue was filtered and washed with 900 ml water and 500 ml IPA. The washed residue was dried under vacuum at 70oC for 6 hrs to obtain of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one having Yield = 0765 kg (73%); and Purity (HPLC) = 99.0%.

The foregoing description of the embodiments has been provided for purposes of illustration and not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
TECHNICAL ADVANCEMENTS
The process for the preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one of the present disclosure described herein above has several technical advantages including, but not limited to, the realization of:
- a simple and environment friendly process for preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one.
- a process for preparation of 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one having high yield, and high purity.
The foregoing description of the specific embodiments fully reveals the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein has been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.
Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired object or results.
Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.
The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values ten percent higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary.
While considerable emphasis has been placed herein on the components and component parts of the preferred embodiments, it will be appreciated that many embodiments can be made and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other changes in the preferred embodiment as well as other embodiments of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.

,CLAIMS:WE CLAIM
1. A process for preparing 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydro pyridine-2-one, said process comprising the following steps:
i) hydrogenating 3-chloro-1-(4-nitrophenyl)-5,6-dihydropyridine-2-one to obtain 3-chloro-1-(4-amino phenyl)-5,6-dihydropyridine-2-one;
ii) reacting 3-chloro-1-(4-amino phenyl)-5,6-dihydropyridine-2-one with 5-bromopentanoyl chloride to obtain 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5,6-dihydropyridine-2-one;
iii) reacting 3-chloro-1-(4-(2-oxopiperidine-1yl)-phenyl)-5, 6-dihydro pyridine-2-one with morpholine to obtain 3-morpholino-1-(4-(2-oxopiperidine-1yl)-phenyl)-5, 6-dihydro pyridine-2-one.
2. The process as claimed in claim 1,

wherein, said hydrogenation in step (i), is carried out in alcohol selected from the group consisting of methanol, ethanol propanol and butanol at a temperature in the range selected from 45 °C to 60 °C and under pressure selected from 5 to 10 kg/m2,

wherein, said reaction in step (ii), is carried out in a fluid medium selected from dichloromethane and dichloroethane, using at least one base selected from the group consisting of sodium carbonate, potassium carbonate, potassium hydroxide, sodium hydroxide, ammonium hydroxide and ammonium carbonate at a temperature in the range selected from 10 °C to 30 °C, and

wherein, said reaction in step (iii), is carried out in a fluid medium selected from the group consisting of chlorobenzene, toluene and benzene at a temperature in the range selected from 80 °C to 120 °C.
3. The process as claimed in claim 2, wherein said alcohol is methanol.
4. The process as claimed in claim 1, wherein said hydrogenation in step (i) is carried out in presence of Raney nickel catalyst in the range of 5wt% to 10 wt% of 3-chloro-1-(4-nitrophenyl)-5,6-dihydropyridine-2-one.
5. The process as claimed in claim 2, wherein said base is a mixture of potassium carbonate and potassium hydroxide.
6. The process as claimed in claim 2, wherein said fluid medium used in step (ii) is dichloromethane.
7. The process as claimed in claim 2, wherein said fluid medium used in step (iii) is chlorobenzene.