发明公开
EP0197432A2 Enantioselective process for producing 1-beta-methylcarbapenem antibiotic intermediates
失效
Enantioselektives Verfahren zur Herstellung von 1-beta-Methylcarbapenem-Antibiotikumzwischenprodukten。
- 专利标题： Enantioselective process for producing 1-beta-methylcarbapenem antibiotic intermediates
- 专利标题（中）： Enantioselektives Verfahren zur Herstellung von 1-beta-Methylcarbapenem-Antibiotikumzwischenprodukten。
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申请号： EP86104146.5申请日： 1986-03-26
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公开(公告)号： EP0197432A2公开(公告)日： 1986-10-15
- 发明人: Shinkai, Ichiro , Salzmann, Thomas N. , Fuentes, Lelia M.
- 申请人： Merck & Co., Inc.
- 申请人地址： 126, East Lincoln Avenue P.O. Box 2000 Rahway New Jersey 07065-0900 US
- 专利权人： Merck & Co., Inc.
- 当前专利权人： Merck & Co., Inc.
- 当前专利权人地址： 126, East Lincoln Avenue P.O. Box 2000 Rahway New Jersey 07065-0900 US
- 代理机构： Abitz, Walter, Dr.-Ing.
- 优先权： US717742 19850329; US717746 19850329; US717342 19850329
- 主分类号： C07D205/08
- IPC分类号： C07D205/08 ; C07D413/06 ; C07D417/06 ; C07D263/22 ; C07D263/26 ; C07D277/12
摘要：
A stereo-controlled process is described for preparing a compound of the formula:
wherein R 1 is, e.g., C 1 -C 4 alkyl, R 2 and R 9 are independently selected from hydrogen, C 1 -C 4 linear, branched or cyclic alkyl, unsubstituted or substituted with fluoro, hydroxy, or protected hydroxy, with the proviso that both R 2 and R 9 are not unsubstituted alkyl, and R 3 is H or easily removable protecting group, comprising the steps of (a) reacting the compound:
wherein L is a leaving group, with the chiral compound:
wherein X 1 and X 2 are independently 0 or S, R 8 is an easily removable enol protecting group, R 4 and R 5 and R 6 are independently selected from H, C 1 -C 4 alkyl, C 7 -C 10 aralkyl, C 6 -C 10 alkaryl, which can be substituted with -OH, -OR 10 , -SH,-SR 10 , where R 10 is C 1 -C 4 alkyl, with proviso that R 4 and R 5 are not identical, in the presence of an organic base and a Lewis acid catalyst to afford the compound:
and then (b) contacting said compound in a solvent therefor, under basic hydrolysis conditions. This compound can be transformed into a carbapenem antibiotic.
wherein R 1 is, e.g., C 1 -C 4 alkyl, R 2 and R 9 are independently selected from hydrogen, C 1 -C 4 linear, branched or cyclic alkyl, unsubstituted or substituted with fluoro, hydroxy, or protected hydroxy, with the proviso that both R 2 and R 9 are not unsubstituted alkyl, and R 3 is H or easily removable protecting group, comprising the steps of (a) reacting the compound:
wherein L is a leaving group, with the chiral compound:
wherein X 1 and X 2 are independently 0 or S, R 8 is an easily removable enol protecting group, R 4 and R 5 and R 6 are independently selected from H, C 1 -C 4 alkyl, C 7 -C 10 aralkyl, C 6 -C 10 alkaryl, which can be substituted with -OH, -OR 10 , -SH,-SR 10 , where R 10 is C 1 -C 4 alkyl, with proviso that R 4 and R 5 are not identical, in the presence of an organic base and a Lewis acid catalyst to afford the compound:
and then (b) contacting said compound in a solvent therefor, under basic hydrolysis conditions. This compound can be transformed into a carbapenem antibiotic.
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