Chlorotrimethylsilane → 3-Bromo-4-(4,4-difluorocyclohexyl)-1,1,1-trifluorobutan-2-one

Temperature

0 °C

4-(4,4-Difluorocyclohexyl)-1,1,1-trifluorobutan-2-one (100 mg, 0.410 mmol) obtained in step 1 was dissolved in DMF (1.0 mL). Under ice-cooled condition, triethylamine (0.110 mL, 0.788 mmol) and chlorotrimethylsilane (0.0570 mL, 0.450 mmol) were added, and the mixture was stirred at 0° C. for 30 minutes. The reaction mixture was extracted with hexane after adding saturated sodium hydrogen carbonate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was then evaporated under reduced pressure. The residue was dissolved in dichloromethane (1.0 mL). Under ice-cooled condition, bromine (73.0 mg, 0.456 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was filtered through a Presep (registered trademark; diatomaceous earth, granular type M, 4.5 g/25 mL) after adding a saturated sodium hydrogen carbonate aqueous solution and sodium thiosulfate aqueous solution. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20) to give 3-bromo-4-(4,4-difluorocyclohexyl)-1,1,1-trifluorobutan-2-one (73.8 mg, yield 56%).

1. additionwere added
2. extractionThe reaction mixture was extracted with hexane
3. additionafter adding saturated sodium hydrogen carbonate
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customThe solvent was then evaporated under reduced pressure
7. dissolutionThe residue was dissolved in dichloromethane (1.0 mL)
8. additionwas added
9. stirringthe mixture was stirred at room temperature for 30 minutes
10. filtrationThe reaction mixture was filtered through a Presep (registered trademark; diatomaceous earth, granular type M, 4.5 g/25 mL)
11. additionafter adding a saturated sodium hydrogen carbonate aqueous solution and sodium thiosulfate aqueous solution
12. customThe solvent was then evaporated under reduced pressure
13. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20)

ORD record

ord-cb4420f3ca4b4254a422d0670f8b0ec6

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09000186B2