Oxygen → HCID 86690091, compound

Temperature

-78 °C

A solution of butyllithium (1.600 mL, 4.00 mmol) was added to cold (−78° C.) solution of diisopropylamine (0.565 mL, 4.00 mmol) in THF (5 mL) under nitrogen and the mixture was stirred at −78° C. 1 h. A solution of ethyl 4,4-difluorocyclohexanecarboxylate (384 mg, 2 mmol) in THF (2 mL) was added at −78° C. and the mixture was stirred for 1 h. The mixture was gradually warmed to −20° C. over 2 h and then recooled to −78° C. and connected to a balloon of oxygen and stirred at −78° C. for 1 h. The reaction mixture was added satd. NaHSO3 solution (5 mL) and allowed to warm to rt and stirred at rt overnight. The reaction mixture was diluted with ether and organic layer separated, washed with water, brine, dried (Na2SO4). Evaporation of the solvent afforded a light yellow oil which was purified by silica gel FCC (DCM) to afford ethyl 4,4-difluoro-1-hydroxycyclohexanecarboxylate as a colorless oil (143 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ 4.28 (q, J=7.3 Hz, 2H), 2.23 (br. s, 1H), 2.19-1.99 (m, 6H), 1.83-1.73 (m, 2H), 1.33 (t, J=1.0 Hz, 3H).

1. custom1 h
2. stirringthe mixture was stirred for 1 h
3. temperatureThe mixture was gradually warmed to −20° C. over 2 h
4. customrecooled to −78° C.
5. stirringstirred at −78° C. for 1 h
6. additionThe reaction mixture was added
7. temperatureto warm to rt
8. stirringstirred at rt overnight
9. customseparated
10. washwashed with water, brine
11. dry with materialdried (Na2SO4)
12. customEvaporation of the solvent
13. customafforded a light yellow oil which
14. customwas purified by silica gel FCC (DCM)

ORD record

ord-763ca7566b3945b3a26fabc2ce5a163b

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09326973B2