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 747022Notes

Reaction equation

HRID 747022 reaction equation
[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]

Participants

6

Reactant 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, compound

Product 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-methanolYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-042a483ee28e4f18ab2e989041aac077
Source dataset
uspto-grants-2008_07
Patent number
US07393858B2

Reaction notes

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