- Efficient alternative synthetic route to diltiazem via (2R,3S)-3-(4- methoxyphenyl)glycidamide
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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.
- Yamada, Shin-ichi,Tsujioka, Ikuko,Shibatani, Takeji,Yoshioka, Ryuzo
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p. 146 - 150
(2007/10/03)
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- Process for preparing 1,5-benzothiazepine derivative
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A novel process for preparing 1,5-benzothiazepine derivative ?II!: STR1 wherein Ring A and Ring B are substituted or unsubstituted benzene ring, and R3 is H, (di-lower alkylamino)-lower alkyl or substituted or unsubstituted piperazinyl-lower alkyl, or a salt thereof, in high yield and in a single step from a novel 3-(2-amino-substituted or unsubstituted phenylthio)-2-hydroxy-3-substituted or unsubstituted phenylpropionamide compound. Said 1,5-benzothiazepine derivative ?II! is useful as an intermediate for preparing medicaments such as diltiazem hydrochloride.
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