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

An effective new route to diltiazem, a representative coronary vasodilator, through (-)-(2R,3S)-3-(4methoxyphenyl) glycidamide [(-)-2] has been achiev ed. The glycidamide (-)-2 was prepared in 43% overall yield by a combinatio n of the enzymatic resolution of methyl (+/-)-(2RS,3SR)-3-(4-methoxyphenyl) glycidate [(+/-)-1] with lipase and the following amidation of (-)-1 with a mmonia. A one-pot synthesis through the treatment of (-)-2 with a-aminothio phenol and a following ring closing reaction efficiently gave a key interme diate of diltiazem synthesis, (2S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphe nyl)-1,5-benzothiazepin-4(5H)-one [cis-(+)-5] in 80% overall yield.