Potassium Carbonate → (R)-2-[2-(5-Fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxirane

HRID 854164Notes

Reaction equation

HRID 854164 reaction equation
[F:1][C:2]([F:28])([F:27])[C@@:3]([CH2:18]SC1C=CC(C)=CC=1)([OH:17])[CH2:4][C:5]([C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[O:15][CH3:16])([CH3:7])[CH3:6].F[B-](F)(F)F.C[O+](C)C.C(=O)([O-])[O-].[K+].[K+].C(=O)(O)[O-].[Na+]>ClCCl.O>[F:14][C:12]1[CH:11]=[CH:10][C:9]([O:15][CH3:16])=[C:8]([C:5]([CH3:7])([CH3:6])[CH2:4][C@:3]2([C:2]([F:28])([F:27])[F:1])[CH2:18][O:17]2)[CH:13]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 16115564(S)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-p-tolylsulfanylmethylpentan-2-ol

Product 1

HCID 11208565(R)-2-[2-(5-Fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxiraneYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-p-tolylsulfanylmethylpentan-2-ol (42.7 g, 102 mmol) in 250 mL of anhydrous dichloromethane was added trimethyloxonium tetrafluoroborate (22.7 g, 153 mmol). The resulting suspension was stirred at room temperature for 4.5 hours. A solution of potassium carbonate (42.4 g, 307 mmol) in 250 mL of water was then added. After 16 hours, the reaction mixture was poured into 200 mL of saturated aqueous sodium bicarbonate solution and extracted with three 400 mL portions of dichloromethane. The combined organic phases were washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography with silica gel (eluted with 0%-2% EtOAc/hexanes) afforded the title compound as a pale yellow oil (28.3 g, 95%).

Workup

  1. waitAfter 16 hours
  2. extractionextracted with three 400 mL portions of dichloromethane
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by column chromatography with silica gel (eluted with 0%-2% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7745338889884fc8ae96258e3775bef4
Source dataset
uspto-grants-2007_08
Patent number
US07256300B2

Reaction notes

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