Patent ID: 7078532

Claim:
A process for preparation of fosinopril sodium of formula (I) predominantly in polymorphic Form-A which comprises (a)(i) reacting a compound of formula (IV) wherein R 7 is lower alkyl of 1–4 carbon atoms with (trans)-4-cyclohexyl-L-proline or salt thereof of formula (V), wherein R 8 is a group easily removable by hydrogenolysis and is benzyl or benzyl substituted at ortho, meta or para positions by an alkyl, alkoxy, alkanoyl, phenyl, nitro or dialkylamino group in the presence of a solvent and a base to give compound of formula wherein R 7 and R 8 are as defined above ii) hydrolysing the alkyl group R 7 in compound of formula (VI) by reaction with a silyl compound in presence of a alkali metal halide and a solvent to give compound of formula (VI), wherein the group R 7 is hydrogen and R 8 is as defined above iii) reacting compound of formula (VI) wherein R 7 is hydrogen and R 8 is as defined above with a compound of formula (VII) wherein X is halogen selected from chlorine, bromine and iodine in the presence of a base and solvent to give compound of formula (II a ) iv) deprotection of the group R 8 in compound of formula (II a ) by reacting with hydrogen in presence of palladium on carbon as catalyst in presence of a solvent to give fosinopril as a mixture of four diastereomers (II A), (II B), (II C) and (II D), b) separating fosinopril diastereomer (II A) from the mixture of four diastereomers (II A), (II B), (II C) and (II D) comprising v) mixing together fosinopril mixture of four diastereomers (II A), (II B), (II C) and (II D) with a cesium metal carrier in the presence of a solvent and crystallisation of the mixture of cesium salts thus formed from the same solvent or a mixture of solvents containing 1–10 moles of water with respect to compound (II A)/(II B)/(II C)/(II D) to give compound of formula (III A) vi) reacting compound of formula (III A) with an acid in the presence of a solvent and water to give the fosinopril diastereomer (II A) and c) converting compound (II A) to fosinopril sodium polymorphic Form-A comprising vii) mixing together compound (II A) with a sodium metal carrier in presence of a solvent or a mixture of solvents to fosinopril sodium of formula (I) and viii) crystallisation of the fosinopril sodium of formula (I) thus formed in the same solvent or mixture of solvents containing water content <0.20% to give fosinopril sodium polymorphic Form-A.