Preparation of diltiazem useful to treat angina involves synthesizing (2R,3S)-(-)-ethyl-2,3-dihydroxy-3-(4-methoxyphenyl)propionate using multifunctional catalyst, ring opening of the cyclic sulfite by 2-aminothiophenol and cyclization

摘要

Preparation of diltiazem (C1) involves synthesizing (2R,3S)-(-)-ethyl-2,3-dihydroxy-3-(4-methoxyphenyl)propionate (I) using a recyclable multifunctional catalyst (A); converting (I) without further crystallization into cyclic sulfite (II); reacting (II) with 2-aminothiophenol in the presence of ferric ion-exchanged clay in xylene to obtain cyclic lactam (III); and N-alkylating (III) and acylating to form (C1). Preparation of diltiazem (C1) involves: (a) synthesizing (2R,3S)-(-)-ethyl-2,3-dihydroxy-3-(4-methoxyphenyl)propionate (I) using a recyclable multifunctional catalyst of formula IE-PdOsW (A); (b) converting (I) without further crystallization into cyclic sulfite (II); (c) reacting (II) with 2-aminothiophenol in the presence of Fe 3 +-exchanged clay in xylene to obtain corresponding cyclic lactam (III); and (d) subjecting the lactam to N-alkylation and acylation to form (C1). IE : ion exchanger. ACTIVITY : Antianginal; Hypotensive; Vasotropic. MECHANISM OF ACTION : Calcium antagonist.