Ethyl-4,4-difluorocyclohexane carboxylate → (4,4-Difluorocyclohexyl)methanol

Temperature

1 °C

Ethyl 4,4-difluorocyclohexanecarboxylate (10 g, 52.03 mmol) was dissolved in THF (100 mL) and cooled to 1° C. under nitrogen atmosphere. LAH (57.2 mL, 57.23 mmol) was added dropwise to the solution at a rate to keep the temperature below 10° C. The resulting mixture was allowed to reach 20° C. and stirred at that temperature for approximately 1 h. The reaction mixture was then cooled to 10° C. and quenched carefully by the sequential slow addition of 2.2 mL of water, 2.2 mL of 15 w/v % aqueous NaOH and 6.6 mL of water and stirred for 30 minutes at 20° C. The solids were removed by filtration and washed with THF. The reaction solution was dried over MgSO4 and evaporated in vacuo to give crude (4,4-difluoro-cyclohexyl)methanol (7.22 g, 92%). 1H NMR (400 MHz, cdcl3) δ 1.21-1.38 (m, 2H), 1.44 (s, 1H), 1.51-1.90 (m, 5H), 2.04-2.18 (m, 2H), 3.52 (d, 2H).

1. customthe temperature below 10° C
2. customto reach 20° C.
3. temperatureThe reaction mixture was then cooled to 10° C.
4. customquenched carefully by the sequential slow addition of 2.2 mL of water, 2.2 mL of 15 w/v % aqueous NaOH and 6.6 mL of water
5. stirringstirred for 30 minutes at 20° C
6. customThe solids were removed by filtration
7. washwashed with THF
8. dry with materialThe reaction solution was dried over MgSO4
9. customevaporated in vacuo

ORD record

ord-893ba5f24d074c3ab6390700ff59c3a4

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08415378B2