Methyl 2-(3,5-bis(trifluoromethyl)phenyl)-2-diazoacetate → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-(methoxycarbonyl)methoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088216ノート

反応式

HRID 2088216 の反応式
[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]#[N:17])[CH2:15][C@@:9]1([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C@H:10]([OH:18])[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+](=[C:27]([C:32]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([C:42]([F:45])([F:44])[F:43])[CH:33]=1)[C:28]([O:30][CH3:31])=[O:29])=[N-]>C1C=CC=CC=1.CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O.[Rh+2].[Rh+2]>[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]#[N:17])[CH2:15][C@@:9]1([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C@H:10]([O:18][C@@H:27]([C:28]([O:30][CH3:31])=[O:29])[C:32]1[CH:33]=[C:34]([C:42]([F:43])([F:44])[F:45])[CH:35]=[C:36]([C:38]([F:39])([F:40])[F:41])[CH:37]=1)[CH2:11][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 2

HCID 54200568Methyl 2-(3,5-bis(trifluoromethyl)phenyl)-2-diazoacetateHCID 69890225(1R*,2R*,5S*,6R*)-8-Benzyl-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol

生成物 1

HCID 86586767(1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-(methoxycarbonyl)methoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane

試薬・触媒・溶媒 2

HCID 152122Dirhodium tetraacetate触媒HCID 241Benzene溶媒2 回

実験手順

A mixture of (1R*,2R*,5S*,6R*)-8-benzyl-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol (Description 31; 7.186 g, 22.6 mmol) and rhodium(II) acetate dimer (0.216 g, 0.452 mmol) in benzene (30 ml) was heated to reflux, and treated slowly with a solution of methyl 2diazo-2-(3,5-bis(trifluoromethyl)phenyl)-acetate [prepared by the method of R. T. Lewis et al. J. Org. Chem., 2000, 65, 2615] (7.7563 g, 24.86 mmol) in benzene (30 ml). After the addition was complete the mixture was concentrated in vacuo and the residue purified by flash column chromatography, eluting with 10-20% ethyl acetate/hexane to give a mixture of diastereomers (6.0 g, 2.6:1 ratio). The major diastereomer was separated by crystallisation with ethyl acetate/hexane to afford the title compound in two crops (3.81 g).

後処理

  1. temperaturewas heated
  2. temperatureto reflux
  3. customprepared by the method of R
  4. additionAfter the addition
  5. concentrationwas concentrated in vacuo
  6. customthe residue purified by flash column chromatography
  7. washeluting with 10-20% ethyl acetate/hexane
  8. customto give
  9. additiona mixture of diastereomers (6.0 g, 2.6:1 ratio)
  10. customThe major diastereomer was separated by crystallisation with ethyl acetate/hexane

出典と根拠

ORDレコード
ord-1f3fae04ad8845ad886aeaac8f940be4
出典データセット
uspto-grants-2004_04
特許番号
US06727249B2

反応ノート

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