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 747022노트

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HRID 747022 반응식
[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]

참가 물질

6

반응물 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, 화합물

생성물 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-methanol수율 80%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-78 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-042a483ee28e4f18ab2e989041aac077
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07393858B2

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