Chlorotrimethylsilane → Cyclohexene, 4,4-difluoro-1-[(trimethylsilyl)oxy]-

Temperature

0 °C

To a solution of N,N-diisopropylamine (3.30 g, 32.6 mmol) in THF (50 mL), n-butyl lithium (1.65 M solution in hexane (18.0 mL, 29.7 mmol) was added dropwise with cooling on ice. The reaction solution was stirred at 0° C. for 30 minutes. Then, 4,4-difluorocyclohexanone (3.60 g, 26.8 mmol) was added thereto at −78° C., and the reaction solution was stirred at −78° C. for 1 hour. To the reaction solution, chlorotrimethylsilane (4.4 mL, 34.8 mmol) and triethylamine (8.0 mL, 57.4 mmol) were added, and the mixture was stirred at −78° C. for 2 hours. To the reaction solution, a saturated aqueous solution of sodium hydrogencarbonate (20 mL) was added, followed by extraction with ethyl acetate (20 mL). The thus obtained organic layer was dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with silica gel chromatography (hexane/ethyl acetate=98:2) to yield the title compound (2.10 g, 56%) as a colorless oil.

1. temperaturewith cooling on ice
2. stirringat −78° C., and the reaction solution was stirred at −78° C. for 1 hour
3. stirringthe mixture was stirred at −78° C. for 2 hours
4. extractionfollowed by extraction with ethyl acetate (20 mL)
5. dry with materialThe thus obtained organic layer was dried over anhydrous sodium sulfate
6. concentrationAfter vacuum concentration
7. customthe residue was purified with silica gel chromatography (hexane/ethyl acetate=98:2)

ORD record

ord-6de295477e624cd5b388352a4b2fb28f

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889741B2