Cyclopentanone → 1-(2-(Trifluoromethyl)phenyl)cyclopentanol

Temperature

-78 °C

A solution of 1-bromo-2-(trifluoromethyl)benzene (0.5 g, 2.222 mmol) in anhydrous THF (10 mL) was cooled to −78° C. (dry ice IPA bath) under argon atmosphere. BuLi (2.5 M in hexanes, 1.068 mL, 2.67 mmol) was added in drops with efficient stirring. The reaction mixture was stirred at −78° C. for 40 min. A solution of cyclopentanone (0.243 g, 2.89 mmol) in anhydrous THF (1.5 mL) was added slowly (in drops) at −78° C. The reaction mixture was stirred at −78° C. for 30 min, gradually brought to room temperature, and stirred for 1 h. The reaction mixture was cooled by an ice bath, quenched with water, and acidified to pH 4-5 by addition of concentrated HCl. The solvent was removed under reduced pressure. The residue was dissolved in methylene chloride, washed with water (2 times), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to give the title compound as an oil (250 mg). LCMS m/z=213.1 [M−H2O+H]+.

1. stirringThe reaction mixture was stirred at −78° C. for 30 min
2. customgradually brought to room temperature
3. stirringstirred for 1 h
4. temperatureThe reaction mixture was cooled by an ice bath
5. customquenched with water
6. additionacidified to pH 4-5 by addition of concentrated HCl
7. customThe solvent was removed under reduced pressure
8. dissolutionThe residue was dissolved in methylene chloride
9. washwashed with water (2 times)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe residue was purified by silica gel chromatography

ORD record

ord-66a1ef7ff2d040c5892b310a393d3a71

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09175320B2