| abstract |
A process is provided for preparing phosphinic acid prodrug intermediates which are useful in preparing phosphinic acid angiotensin-converting enzyme inhibitors which method includes the step of coupling a phosphonous acid or its ester of the structuren wherein R is H or lower alkyl and R 1 is lower alkyl, aryl, arylalkyl, cycloalkyl or cycloalkyl-alkyl, with an alkylating agent of the structuren wherein Hal is Cl, Br or I, n is 0 or 1, R 2 is H or lower alkyl, and Z is H, lower alkyl, -CO 2 R 3 (wherein R 3 is H or lower alkvl.n (wherein R" is H, lower alkyl, aryl or arylalkyl),-CN, or-n (wherein R 5 and R 6 may be the same or different and are selected from the group consisting of H, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkylalkyl and at least one of R 5 and R 6 is other than H, or R 5 and R 6 can be taken with the N-atom to form a 5-, 6- or 7-membered heterocyclic ring which 5-, 6- or 7-membered N-containing ring may or may not contain a C0 2 R 3 group and which 5- or 6-membered N-containing ring may or may not be fused to an aryl ring), in the presence of a silylating agent, to form the phosphinic acid intermediate of the structure |