1. An in-situ process for the preparation of a-chloroketones represented by the Formula (V): (Formula Removed) wherein R is selected from the group consisting of alkyl, substituted alkyl, aryl and substituted aryl and R1 is a protecting group for the amino function comprising converting a compound of Formula (I) (Formula Removed) to an activated intermediate compound of Formula (II) (Formula Removed) which in turn is converted to an aryl ester compound of Formula (III) (Formula Removed) reacting the compound of Formula (III) with a compound of Formula (VIII) with a suitable single solvent (Formula Removed) to provide a compound of Formula (IV) (Formula Removed) reacting the compound of Formula (IV) with a source of suitable chloride and a suitable organic acid to provide the compound of Formula (V).

2. The in situ process as claimed in claim 1, wherein said solvent is toluene.

3. The in situ process as claimed in claim 1, wherein said source of chloride is lithium chloride.

4. The in situ process as claimed in claim 1, wherein said organic acid is methanesulfonic acid.

5. The in situ process as claimed in claim 1, wherein the reaction of said keto ylide compound represented by Formula (V) is carried out in a suitable organic solvent.

6. The in situ process as claimed in claim 5, wherein said organic solvent is selected from the group consisting of tetrahydrofuran, toluene and acetonitrile.

7. The in situ process as claimed in claim 1, wherein the activating agents to prepare the compound of Formula (II) from Formula (I) are selected from the group consisting of t-Boc-anhydride, Isopropyl alcohol (IPA), water, sodium hydroxide, and ethyl acetate (EtOAc).

8. The in situ process as claimed in claim 1, wherein the activating agents to prepare the compound of Formula (III) from Formula (II) are selected from the group consisting of P-Nitrophenol, dicyclohexylcarbodimide, ethyl aceteate (EtOAc) and Hexane.

9. The in situ process as claimed in claim 1, wherein the activating agents to prepare the compound of Formula (IV) from Formula (III) are selected from the group consisting of Trimethyl sulfoxonium iodide (TMSOI), trimethyl sulfoxonium bromide, trimethylsulfoxonium chloride, Sodium ter. butoxide, K-t-Amylate, toluene and MDC.

10. The in situ process as claimed in claim 1, wherein the activating agents to prepare the compound of Formula (V) from Formula (IV) are selected from the group consisting of Lithium chloride, methanesulphonic acid, tetrahydrofuran (THF) and methyl tert-butyl ether (MTBE).

11. The compound of formula (V) as claimed in any of the preceding claims 1 to 10, for the preparation of epoxy compound represented by formula (VII) (Formula Removed)

RELATED APPLICATION INFORMATION
This application claims priority from Indian provisional Patent Application No. 1608/DEL/2010 dated on July 8, 2010. The entire content of which is incorporated herein by this reference. The applicants claim the benefit of this provisional application.
FIELD OF THE INVENTION
The present invention relates to α-chloroketone derivatives. More particularly, the present invention relates to a novel in situ process for the preparation of α-N-acyl-α'-chloroketones. The α-chloroketones produced in accordance with the process of the Invention are precursors of epoxide compounds present in many molecules therapeutically useful as inhibitors of Angiotensin Converting Enzyme (ACE), rennin and HIV-proteases.
BACKGROUND OF THE INVENTION
The a-chloroketone derivatives in addition to their own activity as irreversible enzyme inhibitors are also useful as intermediates in the synthesis of molecules that are inhibitors of ACE, rennin and HIV-proteases. The activity of such molecules against HIV-protease makes them valuable in the treatment of retroviral infections such as AIDS. The activity of such molecules and their use are disclosed in US Patent No. 5849911, the disclosure of which is incorporated herein by reference.
In view of α-N-acyl-α'-chloroketones importance and synthetic utility, a number of methods have been described for the preparation of α-chloroketones. However, such methods involve the use of dangerous as well as expensive reagents (e.g., diazomethane) that are not suitable for commercial production, or they do not provide the requisite level of chiral purity in the α-chloroketone product and also result in lower yield. Further, such methods are multi-staged reactions in that the reaction intermediates are isolated and crystallized at every step, which increases

the manufacturing cost. Therefore, such methods are not advantageous from the industrial viewpoint.
Accordingly, there is a constant need for additional methods for the preparation of a-chloroketones, particularly for the preparation of substantially chirally pure a-chloroketones from amino acids and more particularly for the preparation of epoxide compounds.
SUMMARY OF THE INVENTION
In one of the preferred embodiments, the present invention is directed to an in situ process for the preparation of α-N-acyl-α'-chloroketones from L-phenylalanine (LPA).
The present invention also relates to an improved process for the preparation of corresponding epoxide compounds that are intermediates in the synthesis of chirally pure therapeutic agents, including, for example, inhibitors of renin, angiotensin converting enzyme (ACE), and HIV proteases. Thus, the present disclosure is directed to processes for the preparation of α-chloroketones from carboxylic acids, and, more particularly, to processes for the preparation of substantially chirally pure and chirally pure a-chloroketones derivatives of amino acids.
Accordingly, in one of the preferred embodiments, the present disclosure describes an improved overall in situ process for the preparation of epoxide compounds represented by the Formula (VII), which method is depicted in Scheme A below:

SCHEME A
(Formula Removed)
Further, in one of the preferred embodiments, the present disclosure describes an in situ process for the preparation of compounds of α-N-acyl-α'-chloroketones represented by the Formula (V) from L-phenylalanine (LPA), which method is depicted in Scheme B below:

SCHEME B
(Formula Removed)
Furthermore, in one of the preferred embodiments, the present disclosure describes a process involving conversion by reduction of the compounds of Formula (V) to an intermediate represented by Formula (VI) that is, in turn treated with a suitable base to convert it to the corresponding epoxide represented by Formula (VII), which method is depicted in Scheme C below:

SCHEME C
(Formula Removed)
Accordingly, one object of the present invention is to provide a process for producing α-N-acyl-α'-chloroketones from L-phenylalanlne (LPA), the process facilitating organic layer or concentrated mass to be taken as such till the step of preparation of corresponding epoxide compounds.
It is another object of the present invention to provide a process that avoids isolation and crystallization at each intermediate steps that have previously been required in the preparation of α-N-acyl-α'-chloroketones and corresponding epoxide compounds.
DETAILED DESCRIPTION OF THE INVENTION
The process of the present invention provides an advantageous in situ process for the synthesis for the α-N-acyl-α'-chloroketones represented by the structural Formula (V) which corresponds to the Formula (V) below:
(Formula Removed)
Wherein R is selected from the group consisting of alkyl, substituted alkyl, aryl and substituted aryl and R1 is a protecting group for the amino function.

The compounds represented by formula (V) are irreversible enzyme inhibitors and are also useful as intermediates in the synthesis of molecules that are inhibitors of ACE, renin and HIV proteases.
As utilized herein, the following terms have the definitions given below. The term "alky!" refers to optionally substituted straight- or branched-chain saturated hydrocarbon groups having from 1 to 7 carbon atoms, preferably from 1 to 4 carbon atoms. The expression "lower alkyl" refers to optionally substituted alkyl groups having from 1 to 4 carbon atoms.
The term "substituted alkyl" refers to an alkyl group substituted by, for example, one to four substituents, such as, halo, trifluoromethyl, trifluoromethoxy, hydroxy, alkoxy, cycloalkyoxy, heterocylooxy, oxo, alkanoyl, aryl, aryloxy, aralkyi, alkanoyloxy, amino, alkylamino, arylamino, aralkylamino, cycloalkylamino, heterocycloamino and disubstituted amino. The definitions given herein for alkyl and substituted alkyl apply as well to the alkyl portion of alkoxy groups.
The term "aryl" refers to monocyclic or bicyclic aromatic hydrocarbon groups having from 6 to 12 carbon atoms in the ring portion, for example, phenyl, naphthyl, biphenyl and diphenyl groups, each of which may be substituted.
The term "aralkyi" refers to an aryl group bonded to a larger entity through an alkyl group, for example, a benzyl radical.
The term "substituted aryl" refers to an aryl group substituted by, for example, one to four substituents such as alkyl; substituted alkyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, alkoxy, cycloalkyloxy, heterocyclooxy, alkanoyl, alkanoyloxy, amino, alkylamino, dialkylamino, aralkylamino, cycloalkylamino, heterocycloamino, alkanoylamino, thiol, alkylthio, cycloalkylthio, heterocyclothio, ureido, nitro, cyano, carboxy, carboxyalkyl, carbamyl, alkoxycarbonyl, alkylthiono, arylthiono, alkysulfonyl, sulfonamido, aryloxy and the like. The substituent may be further substituted by one or more members selected from the group consisting of halo, hydroxy, alkyl, alkoxy, aryl, substituted alkyl, substituted aryl and aralkyi.

The term "protecting group on the amino function" refers to an art-recognized group of moieties that can be attached to an amino group to keep it from being involved in reactions taking place elsewhere on the moiety to which it is attached. Preferred among such groups is t-butoxycarbonyl (BOC), but art-recognized amino function protecting groups, generally alkoxycarbonyl or aryloxycarbonyl groups, such as benzyloxycarbonyl, can be used as well.
The term "Ylide" as used herein refers to a neutral compound that contains two adjacent atoms bearing formal positive and negative charges.
Formation of α-N-acvl-α'-chloroketones:
According to the in situ process disclosed in Scheme B for the preparation of a-N-acyl-α'-chloroketones represented by the structural Formula (V) above, the starting material L-phenylalanine (LPA) represented by the Formula (I) is converted to an activated intermediate t-Boc-L-phenylalanine compound represented by the Formula (H) above, which in turn is converted to an aryl ester compound N-t-Boc-L-phenylanine-4-nitrophenylester represented by the Formula (III) above.
Further, in accordance with the in situ process of the present invention, aryl ester represented by Formula (III) above is treated with a sulfur ylide, i.e. a compound containing a function represented by the formula (VIII):
(Formula Removed)
in the presence of a suitable co-solvent, preferably a single co-solvent, such as toluene to produce an intermediate keto ylide intermediate compound (3S)-2-Oxo-N-t-Boc-3-amino-4-phenylbutylide dimethylsulphoxonium represented by the Formula (IV) above.:

The keto ylide intermediate compound represented by formula (IV) above is then converted to the subject α-N-acyl-α'-chloroketones represented by the structural Formula (V) by reaction with a source of chloride, preferably a basic source of chloride, most preferably lithium chloride, and an organic acid, for example, methanesulfonic acid. The treatment with the source of chloride is carried out in an organic solvent such as tetrahydrofuran, toluene or, preferably, acetonitrile. The reaction is initiated at low temperature i.e. from about 0°C to about 5°C. As the reaction proceeds, however the temperature is raised to about 65°C. Reaction of the keto ylide represented by formula VIII above with a lithium chloride and methansulfonic acid to yield α-Chloroketone.
The sulphur ylide reagent represented by Formula (VIII) above is conveniently prepared from a sulfoxonium salt by reaction with a suitable base in an organic solvent. Suitable sulfoxonium compounds include trialkyi sulfoxonium halides, such as trimethylsulphoxonium iodide, trimethyisuphoxonium bromide, trimethylsulphoxonium chloride. Preferable bases include for example sodium hydride, potassium tert. Butoxide, potassium tert amylate, sodium ter.butoxide with the later being particularly preferred. The reaction is carried out in an organic solvent such as dimethylformamide, tetrahydrofuran or preferably toluene with mild heating, i.e. at a temperature of from about 60°C to about 80°C, preferably about 70°C.
Formation of Epoxide compounds:
The α-N-acyl-α'-chloroketones represented by formula (V) above, in addition to their own activity as irreversible enzyme inhibitors, are important intermediates in the synthesis of molecules that are inhibitors of Angiotensin Converting Enzyme (ACE), renin and HIV proteases. The activity of such molecules against HIV proteases makes them very valuable in the treatment of retroviral infections such as AIDS. Thus, as depicted in Scheme C, the subject α-N-acyl-α'-chloroketones represented by formula (V) are converted by reduction to an intermediate compound represented by the Formula (VI) above namely (2S, 3s)-1-Chloro-2hydroxy-3N-(tert-butoxy carbonyl) Amino-4-phenyl butane. That in turn is treated with a suitable base to

convert it to the corresponding to the corresponding epoxide (BCPB) compound represented by formula (VII) as above.
Preferably, ethanol and toluene are used for reduction step, after completion of reaction organic layer is quenched with acetic acid and filtered at -10°C.
The epoxide (BCPB) compounds represented by formula (VII) are intermediates that can be converted to the important HIV protease inhibitor 2,5,6,10,13-pentaazaretetradecanedioic acid, 3,12-bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylme thyl)-6{[4-(2-pyridinyl)phenyl]methyl}-dimethyl ester (3S,8S,9S,12S) as disclosed in US Patent No. 5849911, the disclosure of which is incorporated herein by reference. The synthesis of the compounds represented by formula (VII) above beginning with the compound represented by formula (I) is an advantageous improvement over synthetic routes known heretofore.
As depicted in the general in situ process of Scheme A above, the isolation and crystallization at each intermediate step is completely avoided. Further, organic layer or concentrated mass is taken as such starting from step 1 next up to step 5, wherein the subject α-N-acyl-α'-chloroketones represented by formula (V) are converted by reduction to an intermediate compound represented by the Formula (VI) above namely (2S, 3S)-1-Chloro-2-hydroxy-3-N-(tert-butoxy carbonyl)-amino-4-phenyl butane which in turn produce corresponding epoxide (BCPB) compounds represented by formula (VII) above.
Further, one of ordinary skill will recognize that a broad range of activating agents can be used to prepare the keto ylides and α-chloroketones which in turn is used to produce corresponding epoxide (BCPB) compounds in accordance with the present disclosure as depicted in above Schemes A, B and C including but not limited to and identified as below with the reaction steps:
Step 1: t-Boc-anhydride, Isopropyl alcohol (IPA), water, sodium hydroxide, hexane, ethyl acetate (EtOAc);
Step 2: P-Nitrophenol, dicyclohexylcarbodimide, ethyl aceteate (EtOAc); Step 3: Trimethyl sulfoxonium iodide (TMSOl), K-t-amylate, toluene, MDC;

step 4: Lithium chloride, methanesulphonic acid, tetrahydrofuran (THF), methyl tert-butyl ether (MTBE);
Step 5: Sodium tetrahydroborate (NaBH4), ethanol, toluene; and Step 6: 10% Sodium hydroxide, acetone.
The following examples are intended to illustrate, but not to limit the invention as disclosed herein:
EXAMPLE 1
Preparation f (S)-[N—1(1-benzvl-2-oxo-3-chloro) propyl] carbamic acid t-butvl ester:
A one liter flask equipped with a large stir bar, a reflux condenser and argon inlet is charged with 1000 gm water and 50 gm sodium hydroxide. There is then added with stirring 200 gm (1.21 mole) L-phenylalanine under agitation at RT. 200 gm Isopropyl alcohol is added. The reaction mixture is cooled to 10-15°C and a solution of Di-tert-butyldicarbonate (317 gm 1.45 mole) in 200 gm IPA is added over one and half hour so that internal temperature remain between 10-15°C. The reaction is stirred at this temperature for about five minutes and then is allowed to warm to 30-35°C over 30 min. The reaction mixture is stirred at 30-35''C for a further 8-10 hrs. HPLC analysis of reaction mixture show complete consumption of L-phenylalanine.
300 gm hexane is added to the reaction mass and the layers are separated. Aq. Layer is extracted with 300 gm hexane and the layers are separated. The combine organic layer with 400 gm saturated sodium bi carbonate solution is extracted and the layers are separated. The combined both the aq. layer and pH is is adjusted to 1-1.5 by adding ~ 240 gm orthophosphoric acid. 350 gm ethylacetate is added and the layers are separated. Aq, layer is extracted with 350 gm ethyl acetate and the layers are separated. The organic layers are combined and washed with 400 gm saturated brine solution and the layers are separated. Charged organic layer containing t-Boc-L-phenylalanine, 4-Nitrophenol (140 gm, 1.00 mole) and 850 gm ethyl acetate in above. The mixture is cooled to about 0-2°C. There is then added with stirring (255 gm, 1.21 mole) DCC in 415 gm Ethyl acetate at about 0-5°C. The reaction is stirred at this temperature for 3 hrs. HPLC analysis of reaction mass show complete consumption of the N-Butoxycarbonyl-L-phenylalanine. Reaction mass is allowed to

warm to 25-30°C over 30 min. Reaction mass is filtered and washed with 300 gm Ethyl acetate. Collecting filtrate and washing, concentrated under vacuum to obtain N-(2-t-butoxycarbonyl)-L-phenylalanine-4-nitrophenyl ester (390 gm, 1.10 mole 83.41% yield) HPLC purity of >98% is obtained. 500 gm Toluene is charged to concentrated mass to obtain slurry.
Charged 2925 gm toluene and potassium ter. amylate (373.54 gm 2.96 mole). The mixture is cooled to 0-5°C. There is then added with stirring trimethylsulfoxonium iodide (669 gm, 3.04 mole) at 10-15°C in 45-60 minutes. The temperature of reaction mass is raised to 70-75°C. The reaction mass is stirred at 70°C for 2 hrs to afford the corresponding Ylide which is reacted in solution without isolation. The reaction mass is cooled to 0-5°C and a slurry of N-(2-t-butoxycarbonyl)-L-phenylalanine-4-nitrophenyl ester (390 gm, 1.10 mole) in 500 gm toluene is added over 1 hr between 0-5°C. The reaction is stirred at this temperature for 30 minutes and then is allowed to warm to ambient temperature over 30 minutes. The reaction mass is stirred at ambient temperature for a further 30 minutes. HPLC analysis of reaction mass show complete conversion of N-(2-t-butoxycarbonyl)-L-phenylalanine-4-nitrophenyl ester.
The reaction mixture is quenched with 1950 gm water and stirred for 15 minutes after which it is concentrated under vacuum to remove toluene. The concentrated mass is extracted with 2925 gm and 585 gm dichloromethane. The combined extracts are washed with 975 gm water and concentrated under vacuum to obtain the product as a light yellow solid (3S)-2-oxo-3-(t-butyloxycarbonylamino)-4-phenylbutylide dimethylsulfoxonium (312 gm, 0.920 mole, 91.09% yield) HPLC purity of 97% is obtained which is carried out to next step without filtration and further purification.
In an inert atmosphere charged 3900 gm THF in above concentrate mass. The reaction mixture is cooled to 0°C and lithium chloride (49.42 gm, 1.17 mole) is added in a single portion. A solution of methanesulfonic acid (103.58 gm, 1.08 mole) in 177.84 gm THF is added over 1 hr so that the internal temperature of the mixture remain between 0 to 2°C.

After which the mixture is allowed to warm to 65-70°C and stirred for 3 hrs. HPLC show complete consumption of the starting material.
Cooling the reaction mass to 40-45°C and distilling out THF under reduced pressure at 40-45°C. Ethyl acetate (1560 gm) in charged in concentrate mass and 5% sodium bicarbonate solution (892.32 gm) is added. The reaction mass is agitated for 30 min and layer is separated. Aqueous layer is extracted with Ethyl acetate (312 gm) and the resultant layer is separated.
Both the organic layers are combined and washed with 10% NaCl solution (780 gm). Ethyl acetate is distilled out completely under reduce pressure at 40-45°C. Charged Hexane (624 gm) in concentrate mass. The mass is cooled to 0-5°C and the resulting solid is filtered and washed with chilled Hexane 31.2 gm. (S)-[N—1(1-benzyl-2-oxo-3-chloro) propyl] carbamic acid t-butyl ester (227.76 gm, 0.765 Mole, 83.13% yield ) 63.22 % yield wrt to L-phenylalanine is obtained.
EXAMPLE 2:
Preparation of (S.S)-rN-(1-benzvl-2-hvdroxv-3-chloro)-propvn carbamic acid t-butvl ester
A solution of (S)-[N—1(1-benzyl-2-oxo-3-chloro) propyl] carbamic acid t-butyl ester (227.76 gm, 0.765 mole) in 1758.31 gm ethanol and 437.30 gm toluene. The reaction mass is cooled to -10°C. Sodiumborohydride (14.76 gm, 0.39 mole) is added lot wise at -10 to -5°C over 1 hr. The temperature is maintained for 3 hrs at -10 to -5°C. The temperature of reaction mass is raised to RT over 45 minutes. The reaction mass is quenched by drop wise addition of 41.73 gm acetic acid. The temperature of reaction mass is raised to 60°C over 30 minutes. Reaction mass is cooled to -10°C in 1-2 hrs and maintained for 6 hrs. The resultant product is filtered at -10°C. Then the product is washed with 227.76 gm toluene and two of 227.76 gm portion chilled water. The resulting product is dried under reduced pressure at 55-60°C for 6-7 hrs to afford (S, S)-[N-(1-benzyl-2-hydroxy-3-chloro)-propyl] carbamic acid t-butyl ester (182.21 gm, 0.609 mole, 79.65% yield) and the HPLC purity of 96% is obtained.

EXAMPLE 3:
Preparation of 1-(1, (R)-oxiranvl-2-(phenvlethvl) carbamic acid-t-butyl ester (BCPB)
(S,S)-[N-(1-benzyl-2-hydroxy-3-chloro)-propyl] carbamic acid t-butyl ester (182.21 gm, 0.609 mole) is dissolved in 1155.88 gm acetone and the solution is cooled to 5°C. 10% aq. sodium hydroxide solution (338.22 gm) is added and the mixture is stirred for 2.5 hrs. HPLC analysis of reaction mass indicate complete conversion of (S, S)-[N-(1-benzyl-2-hydroxy-3-chloro)-propyl] carbamic acid t-butyl ester. Thereafter, the reaction mass is filtered and layers arer separated. Then water (2847 gm) is slowly added to the organic layer. The resulting slurry mass is cooled to 5°C. and filtered at 5°C. The resultant solid is washed with 113.88 gm chilled water. The solid is dried under vacuum to afford 1-(1, (R)-oxiranyl-2-(phenylethyl) carbamic acid-t-butyl ester 132.10 gm, 0.502 mole, 82.62% yield) and thus the HPLC purity of 99.13% is obtained.
From the foregoing description, it will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto without departing from the spirit or scope of the invention as set forth herein. The terms and expressions which have been employed are used as terms of description and not of limitation, and it is not intended to exclude any equivalents of the features shown or described or portions thereof, since it is recognized that various modifications are possible within the scope of the invention claimed. Accordingly, it is not intended that the scope of the foregoing description be limited to the exact description set forth above, but rather that such description be construed as encompassing all of the features of patentable novelty that reside in the present invention, including all the features and embodiments that would be treated as equivalents thereof by those skilled in the art.

WE CLAIM:
1. An in-situ process for the preparation of a-chloroketones represented by the Formula (V):
(Formula Removed)
wherein R is selected from the group consisting of alkyl, substituted alkyl, aryl and substituted aryl and R1 is a protecting group for the amino function comprising converting a compound of Formula (I)
(Formula Removed)
to an activated intermediate compound of Formula (II)
(Formula Removed)
which in turn is converted to an aryl ester compound of Formula (III)

(Formula Removed)
reacting the compound of Formula (III) with a compound of Formula (VIII) with a suitable single solvent
(Formula Removed)
to provide a compound of Formula (IV)
(Formula Removed)
reacting the compound of Formula (IV) with a source of suitable chloride and a suitable organic acid to provide the compound of Formula (V).
2. The in situ process as claimed in claim 1, wherein said solvent is toluene.
3. The in situ process as claimed in claim 1, wherein said source of chloride is lithium chloride.
4. The in situ process as claimed in claim 1, wherein said organic acid is methanesulfonic acid.

5. The in situ process as claimed in claim 1, wherein the reaction of said keto ylide compound represented by Formula (V) is carried out in a suitable organic solvent.
6. The in situ process as claimed in claim 5, wherein said organic solvent is selected from the group consisting of tetrahydrofuran, toluene and acetonitrile.
7. The in situ process as claimed in claim 1, wherein the activating agents to prepare the compound of Formula (II) from Formula (I) are selected from the group consisting of t-Boc-anhydride, Isopropyl alcohol (IPA), water, sodium hydroxide, and ethyl acetate (EtOAc).
8. The in situ process as claimed in claim 1, wherein the activating agents to prepare the compound of Formula (III) from Formula (II) are selected from the group consisting of P-Nitrophenol, dicyclohexylcarbodimide, ethyl aceteate (EtOAc) and Hexane.
9. The in situ process as claimed in claim 1, wherein the activating agents to prepare the compound of Formula (IV) from Formula (III) are selected from the group consisting of Trimethyl sulfoxonium iodide (TMSOI), trimethyl sulfoxonium bromide, trimethylsulfoxonium chloride, Sodium ter. butoxide, K-t-Amylate, toluene and MDC.
10. The in situ process as claimed in claim 1, wherein the activating agents to prepare the compound of Formula (V) from Formula (IV) are selected from the group consisting of Lithium chloride, methanesulphonic acid, tetrahydrofuran (THF) and methyl tert-butyl ether (MTBE).
11. The compound of formula (V) as claimed in any of the preceding claims 1 to 10,
for the preparation of epoxy compound represented by formula (VII)
(Formula Removed)