Borane;tetrahydrofuran → (R)-2-[3-(Trifluoromethyl)phenyl]oxirane

HRID 530581Notes

Reaction equation

HRID 530581 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=1)=[O:4].B.C1COCC1>O1CCCC1.C1(C)C=CC=CC=1>[F:12][C:11]([F:14])([F:13])[C:7]1[CH:6]=[C:5]([C@@H:3]2[CH2:2][O:4]2)[CH:10]=[CH:9][CH:8]=1

Participants

5

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 27783862-Bromo-1-[3-(trifluoromethyl)phenyl]ethan-1-one

Product 1

HCID 22823242(R)-2-[3-(Trifluoromethyl)phenyl]oxiraneYield 90.5%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Solutions of 4.006 g (15 mmol) of 2-bromo-1-(3-trifluoromethylphenyl)-ethanone, 15 mL of anhydrous tetrahydrofuran and 15 mL of 1M borane-THF in tetrahydrofuran were added simultaneously to a stirring solution of 1.5 mL of 1M (R)-(3aR)-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole in toluene and 15 mL of anhydrous tetrahydrofuran, cooled in an ice water bath at ca. 15 degrees, over 12.5 minutes. The cooling bath was removed and the mixture stirred at room temperature. After 1.5 h, ca. 0.48 g of methanol was added dropwise (gas evolution) and the mixture stirred for 5 minutes, then 15 mL of 2 M sodium hydroxide was added over 3 minutes. The mixture was stirred at room temperature. After 1.5 h, the mixture was concentrated under reduced pressure to remove the tetrahydrofuran, and the remaining aqueous phase was extracted twice with diethyl ether. The combined ether extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 2.553 g (90%) of (R)-2-(3-trifluoromethyl-phenyl)oxirane as a light amber liquid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.87 (dd, J=5.27, 2.51 Hz, 1H) 3.12 (dd, J=5.27, 4.02 Hz, 1H) 4.04 (dd, J=4.27, 2.51 Hz, 1H) 7.54-7.58 (m, 2H) 7.60 (s, 1H) 7.62-7.67 (m, 1H).

Workup

  1. temperaturecooled in an ice water bath at ca. 15 degrees, over 12.5 minutes
  2. customThe cooling bath was removed
  3. additionca. 0.48 g of methanol was added dropwise (gas evolution)
  4. stirringthe mixture stirred for 5 minutes
  5. addition15 mL of 2 M sodium hydroxide was added over 3 minutes
  6. stirringThe mixture was stirred at room temperature
  7. waitAfter 1.5 h
  8. concentrationthe mixture was concentrated under reduced pressure
  9. customto remove the tetrahydrofuran
  10. extractionthe remaining aqueous phase was extracted twice with diethyl ether
  11. dry with materialThe combined ether extracts were dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e5385bda748744e588beb30380c3b9f2
Source dataset
uspto-grants-2016_05
Patent number
US09353096B2

Reaction notes

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