Ethyl Acetate → (2R,3R,4R,alphaRS)-alpha-(3-Buten-1-yl)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}tetrahydro-3-phenyl-2H-pyran-4-methanol

HRID 747022ノート

反応式

HRID 747022 の反応式
[CH2:1]([Mg]Br)[CH2:2][CH:3]=[CH2:4].[F:7][C:8]([F:37])([F:36])[C:9]1[CH:10]=[C:11]([C@H:19]([O:21][C@@H:22]2[C@@H:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C@H:26]([CH:34]=[O:35])[CH2:25][CH2:24][O:23]2)[CH3:20])[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1.[Cl-].[NH4+].C(OCC)(=O)C>O1CCCC1>[CH2:1]([CH:34]([C@@H:26]1[CH2:25][CH2:24][O:23][C@H:22]([O:21][C@@H:19]([C:11]2[CH:10]=[C:9]([C:8]([F:36])([F:7])[F:37])[CH:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=2)[CH3:20])[C@H:27]1[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[OH:35])[CH2:2][CH:3]=[CH2:4]

参加物

6

反応物 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 86601738(2R,3R,4R)-2-[(1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy]-3-phenyl-tetrahydropyran-4-carbaldehydeHCID 178418797HCID 178418797、化合物

生成物 1

HCID 86606916(2R,3R,4R,alphaRS)-alpha-(3-Buten-1-yl)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}tetrahydro-3-phenyl-2H-pyran-4-methanol収率 80%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

3-Butenylmagnesium bromide (0.5M in tetrahydrofuran, 75 mL, 37.5 mmol) was added slowly to a stirred, cooled −78° C. solution of (2R,3R,4R)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}tetrahydro-3-phenyl-2H-pyran-4-carboxaldehyde (WO 00/56727A1; 11.1 g, 24.9 mmol) in tetrahydrofuran (125 mL). The mixture was stirred at −78° C. for 3 hours, then at room temperature for 1.5 hour. Saturated aqueous ammonium chloride (20 mL) was added slowly, followed by ethyl acetate (300 mL). The layers were separated and the organic layer was washed with brine (100 mL). The combined aqueous layers were extracted with ethyl acetate (100 mL), the combined organic layers were dried (Na2SO4), and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane/EtOAc (97:3 increasing to 80:20), to give the title compound (8:1 mixture of alcohol diastereoisomers) as a colorless oil (10 g, 80%).

後処理

  1. waitat room temperature for 1.5 hour
  2. customThe layers were separated
  3. washthe organic layer was washed with brine (100 mL)
  4. extractionThe combined aqueous layers were extracted with ethyl acetate (100 mL)
  5. dry with materialthe combined organic layers were dried (Na2SO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel
  8. washeluting with hexane/EtOAc (97:3 increasing to 80:20)

出典と根拠

ORDレコード
ord-042a483ee28e4f18ab2e989041aac077
出典データセット
uspto-grants-2008_07
特許番号
US07393858B2

反応ノート

読み込み中…