FIELD OF INVENTION
The present invention relates to A process, amenable for large scale production of 9-hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I), illustrated in Fig.i in more than 97% purity by HPLC and its conversion in to its hydrochloride salt. (IV), illustrated in Fig.4.
9-Hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I) is used, in the synthesis of Paliperidone (II), illustrated in Fig.2 an anti-psychotic agent disclosed in EP0368388.
BACKGROUND AND PRIOR ART
The US patent no.5688799 discloses a process for g-hydroxy-3- (2-hydroxyethyl)~2-methyl-4H- pyrido [1,2a] primidin-4-one (III), illustrated in Fig.3 in which 2-amino-3-hydroxy pyridine is reacted with 2-acetyl butyrolactone in the presence of p-toluene sulfonic acid in xylene.
The intermediate III is then converted into 9-hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I) by reacting the same with thionyl chloride in dimethyl formamide.
Published application WO 2006/027370 describes a modified process for preparation of 9-hydroxy-3- (2-hydroxyethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (III) involving the reaction of 3-hydroxy-2-amino pyridine with 2-acetyl butyrolactone in chloro benzene as a solvent and p-toluene sulfonic acid as a catalyst. The product is isolated by the work up involving the addition of alcoholic solvent and filtration of the reaction mixture at 9O-95°C.
The process involves hazard of filtration of reaction mixture containing flammable solvents at 9O-95°C which poses problems in scale up operations.

SUMMARY OF THE INVENTION:
9-Hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I) is used in the synthesis of Paliperidone (II), illustrated in Fig.2 an anti-psychotic agent, disclosed in EP0368388.
In this present embodiment,
The invention provides for an efficient, single stage process for synthesis of 9-hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I) starting from 2-amino-3-hydroxy pyridine and 2-acetyl butyrolactone as depicted in scheme 1, illustrated in Fig.5 and conversion of the same (I) to its hydrochloride salt (IV) by the reaction with gaseous or alcoholic HC1 in alcoholic or aromatic solvents
SCHEME-I
The process of the instant invention comprises the steps of
a) Reacting 2-amino-3-hydroxy pyridine with 2-acetyl butyrolactone in phosphorous oxy chloride at temperature between 200 - 7O°C.
b) Quenching reaction mass in mixture of ice and water.
c) Adjusting pH to 4-6 with base.
d) Filtering the separated solid 9-hydroxy-3- (2-chloroethyl)-2- methyl-4H-pyrido [1,2a] primidin-4-one (I) and drying same by the conventional methods.
e) Reacting 9-hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4- one (I) with alcoholic or gaseous hydrogen chloride in alcoholic or aromatic solvents to yield hydrochloride salt (IV)of 9~hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I).
DETAIL DESCRIPTION OF THE INVENTION
The present invention provides for an efficient process for synthesis of 9-hydroxy-3-(2-chloroethyl)2- methyl-4H- pyrido [1,2a] primidin-4-one (I). The process is simple, amenable for scale up, yields 9-hydroxy-3- (2-chloroethyl)-2- methyl-4H-pyrido [1,2a] primidin-4-one (I) with purity more than 97% by HPLC. The 9-hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I) thus

obtained, can be converted to its hydrochloride salt (IV)by the process described herewith.
The process is described in more details below-
2-Amino-3-hydroxy pyridine is reacted with i to 2 equivalents of 2-acetyl butyrolactone in 2.4 - 7 equivalents of phosphorous oxy chloride at temperature of 2O°-7O°C. The reaction mass after completion of the reaction is quenched into a mixture of ice and water. The pH of the acidic mixture is adjusted to 4-6 with base. The separated solid is filtered and dried using conventional drying techniques like vacuum oven drying to yield 9-hydroxy-3- (2-chloroethyl)-2- methyl~4H- pyrido [1,2a] primidin-4-one (I) in more than 97% purity by HPLC. The 9-hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I) thus obtained is taken in alcoholic and /or aromatic solvent and treated with hydrogen chloride in gaseous form or its solution in alcoholic solvent to yield its hydrochloride salt. The invention is further illustrated by following non-limiting examples.
Examples:
1. Preparation of 9-Hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I)


2. Preparation of 9-Hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one .Hydrochloride(IV)
9-Hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one 2.35 parts was added into 1300 parts of methanol which was then acidified and the pH was adjusted with 500 part of methanolic HC1( 10-13%) to 0-1. The reaction mass was concentrated to thick slurry, filtered and washed with 100 parts chilled methanol. The product was dried at 6o°C under vacuum ( 700 mm Hg)to yield 219 parts of 9-Hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one hydrochloride(IV) with HPLC purity above 98%.
1H -NMR (D20): δ 2.414 (3H,s), δ 2.723 (2H,t) δ 3.904 (2H,t), δ 7-602 (1H,m), δ 7-747 (1H,d) δ 8.732 (1H,d).
We claim
1. A process for synthesis of 9-hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I)) with purity of more than 97% and its conversion in to its hydrochloride salt (IV)comprising steps of
a) reacting 2-amino-3-hydroxy pyridine with 1-2 equivalent of 2-acetyl butyrolactone in 2.4 to 7 equivalents of phosphorus oxy chloride at temperature of 2O°-7O°C to obtain a reaction mass.
b) quenching of reaction mass into mixture of ice and water to obtain a reaction mixture.
c) adjusting the pH of reaction mixture to 4-6 with base
d) isolating of separated solid by filtration
e) drying using conventional techniques like vacuum oven drying to give 9- hydroxy-3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I)
f) reacting 9-hydroxy~3- (2-chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4- one (I) thus obtained with alcoholic or gaseous hydrogen chloride in alcoholic or aromatic solvents to yield hydrochloride salt (IV)of 9-hydroxy~3- (2- chloroethyl)-2- methyl-4H- pyrido [1,2a] primidin-4-one (I).

2. A process as claimed in claim la) where the reaction is carried out at 3O°-7O°C temperature.
3. A process as claimed in claims la) and 2 where the reaction is carried out at 300- 6o°C temperature.
4. A process as claimed in claim la) where 1- 1.3 equivalents of 2-acetyl butyrolactone is used per equivalent of 2-amino-3-hydroxy pyridine.
5. A process as claimed in claim la) where 3 to 6 equivalent of phosphorus oxy chloride are used per equivalent of 2-amino-3-hydroxy pyridine.
6. A process as claimed in claim la) and 5 where 3-4 equivalents of phosphorus oxy chloride per equivalent of 2-amino-3-hydroxy pyridine are used for reaction.

7. A process of claimed in claim lc) where the pH of the reaction mixture is adjusted to 5-6.
8. A process as claimed in claim lc) where base used is aqueous ammonia,
9. A process as claimed in claim IC) where base used is aqueous sodium hydroxide. 10. A process as claimed in claim l where base used is aqueous potassium Hydroxide
n. A process as claimed in claim le) where the alcoholic solvent is selected from group comprising of methanol, ethanol, n-propanol, 2-propanol , n-butanol and t-butanol.
12. A process as claimed in claim le) and nwhere the aromatic solvent is selected from group comprising of toluene and xylene .
13. A process as claimed in claim le) and 11 where the alcoholic solvent is methyl alcohol.
14. A process as claimed in claim le) and 11 where the alcoholic solvent is methyl alcohol and the methanolic hydrogen chloride is used.
15. A process as claimed in claim le) and 12 where toluene is used as solvent and methnolic hydrogen chloride is used.