发明申请
US20070135449A1 Process for selective synthesis of enantiomers of substituted 1-(2-amino-1-phenyl-ethyl)-cyclohexanols 失效
选择性合成取代的1-(2-氨基-1-苯基 - 乙基) - 环己醇的对映异构体的方法

  • 专利标题: Process for selective synthesis of enantiomers of substituted 1-(2-amino-1-phenyl-ethyl)-cyclohexanols
  • 专利标题(中): 选择性合成取代的1-(2-氨基-1-苯基 - 乙基) - 环己醇的对映异构体的方法
  • 申请号: US11633207
    申请日: 2006-12-04
  • 公开(公告)号: US20070135449A1
    公开(公告)日: 2007-06-14
  • 发明人: Paige MahaneyMadelene AntaneJerry Sun
  • 申请人: Paige MahaneyMadelene AntaneJerry Sun
  • 申请人地址: US NJ Madison
  • 专利权人: Wyeth
  • 当前专利权人: Wyeth
  • 当前专利权人地址: US NJ Madison
  • 主分类号: A61K31/495
  • IPC分类号: A61K31/495 C07D241/04 C07C62/30
Process for selective synthesis of enantiomers of substituted 1-(2-amino-1-phenyl-ethyl)-cyclohexanols
摘要:
A process for the enantioselective synthesis of an (S)— or (R)-1-[2-dimethylamino)-1-(methoxyphenyl)ethyl]cyclohexanol and analogues or salt thereof are described. The method involves the steps of (a) reacting an (S) or (R) 4-benzyloxazolidinone with a mixed anhydride of a methyoxyphenylacetic acid under conditions which form a oxazolidinone, (4S)— or (4R)-4-benzyl-3-[methyoxyphenyl]acetyl]-oxazolidin-2-one, (b) treating the (4S)— or (4R)-4-benzyl-3-[(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one with an aprotic amine base and titanium chloride in a chlorinated solvent under conditions which permit formation of the corresponding anion, (c) mixing the corresponding anion with titanium chloride and cylcohexanone under conditions which permit an aldol reaction to form the corresponding (4S)— or (4R)-4-benzyl-3-[(2R)-2-(1-hydroxycyclohexyl)-2-(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one, (d) hydrolyzing the (4S)— or (4R)-4-benzyl-3-[(2R)-2-(1-hydroxycyclohexyl)-2-(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one to form a chiral acid (2S or 2R)-(1-hydroxycyclohexyl)-methoxyphenyl)acetic acid, (e) coupling the chiral phenylacid to a secondary amine to form an amide, and (f) reducing the amide to form an (S) or (R) 1[2-dimethylamino)-1-(methoxyphenyl)ethyl]cyclohexanol or a salt thereof.
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