Efficient alternative synthetic route to diltiazem via (2R,3S)-3-(4- methoxyphenyl)glycidamide

Article abstract of DOI:10.1248/cpb.47.146

An effective new route to diltiazem, a representative coronary vasodilator, through (-)-(2R,3S)-3-(4-methoxyphenyl)glycidamide [(-)-2] has been achieved. The glycidamide (-)-2 was prepared in 43% overall yield by a combination of the enzymatic resolution of methyl (±)2(2RS,3SR)-3-(4- methoxyphenyl)glycidate [(±)-1] with lipase and the following amidation of (-)-1 with ammonia. A one-pot synthesis through the treatment of (-)-2 with 2-aminothiophenol and a following ring closing reaction efficiently gave a key intermediate of diltiazem synthesis, (2S,3S)-2,3-dihydro-3-hydroxy-2-(4- methoxyphenyl)-1,5-benzothiazepin-4(5H)-one [cis-(+)-5] in 80% overall yield.

Full text of DOI:10.1248/cpb.47.146

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NII-Electronic Library Service

NII-Electronic Library Service