Synthesis of Fosinopril Sodium

Two conceptually different approaches to the tra 5-4-cyclohexylproline fragment have been disclosed by the Squibb process group. The first route relies on a stereoselective alkylation for installation of the cyclohexyl substituent (Thottathil et al., 1986). L-Pyroglutamic acid (62) was reduced using literature methods to give the hydroxymethyl 

TABLE 10.2. In vitro and In vivo Activities for Phosphinic Acids 59-61 

Patchett, A. A. (1993). Enalapril and Lisinopril . Chronicles of Drug Discovery, 3 125-162. 

Geiger, R., and Gaul, H. (1984b). Tetrahedron Lett., 25 4479-4482. 

Geiger, R., Henning, R., and Urbach, R. (1984a). Arzneim.-Forsch, 34 1399-1401. 

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In view of reusabiUty of the catalyst and easy separation/purification of the products, the new procedure is advantageous in practical applications, e.g., the synthesis of fosinopril sodium (Scheme 21). 

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