| abstract |
A method is provided for preparing phosphinic acid compounds, which are useful in preparing certain angiotensin converting enzyme inhibitors, which have the formula <IMAGE> wherein R1 is lower alkyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl; R2 is hydrogen, lower alkyl or arylalkyl; X is hydrogen, lower alkyl or phenyl; Y is hydrogen, lower alkyl, phenyl or alkoxy, or together X and Y are -(CH2)2-, -(CH2)3-, -CH=CH-, or <IMAGE> and n is 0 or 1 including salts thereof and stereoisomers thereof, which method includes the steps of reacting a phosphinic acid ester of the structure <IMAGE> wherein R3 is a group removable by hydrogenolysis such as benzyl or substituted benzyl, with a halo ester of the structure <IMAGE> in the presence of an organic base to form a phosphinic acid ester of the structure <IMAGE> hydrogenating the above ester to form a diastereomic mixture of a phosphinic acid of the structure <IMAGE> recrystallizing to recover the preferred racemic mixture and resolving same employing a resolving agent, preferably L-cinchonidine, to form the corresponding resolved salt which may be acidified to the corresponding acid. In addition, novel intermediates which are acids and salts as described above are also provided. |