Patent ID: 7078532
Filing Date: 2006-07-18
Classification: C07F

Abstract:
1. 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 wherein R wherein R ii) hydrolysing the alkyl group R iii) reacting compound of formula (VI) wherein R wherein X is halogen selected from chlorine, bromine and iodine in the presence of a base and solvent to give compound of formula (II iv) deprotection of the group R 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.