Methyl iodide → HCID 86690086, compound

Temperature

-78 °C

A solution of n-butyl lithium (1.250 mL, 2.000 mmol) was added to a cold (−78° C.) solution of diisopropylamine (0.283 mL, 2.000 mmol) in THF under nitrogen and the mixture was stirred at −78° C. 1 h. A solution of ethyl 4,4-difluorocyclohexanecarboxylate (192 mg, 1 mmol) in THF (1 mL) was added at −78° C. The reaction mixture was stirred at −78° C. for 1 h and then gradually warm to −20° C. over 2 h. Then neat iodomethane (0.138 mL, 2.200 mmol) was added at −78° C. and the mixture was allowed to warm to rt and stirred at rt overnight. The reaction was quenched with satd. NH4Cl and extracted with EtOAc and the organic phase was washed with water, brine, dried (Na2SO4). Evaporation of the solvent afforded ethyl 4,4-difluoro-1-methylcyclohexanecarboxylate (222 mg) as a light brown oil which was dissolved in EtOH and was added a solution of KOH (112 mg, 2.000 mmol) in water (2.00 mL). The reaction mixture was heated to reflux overnight, then cooled and acidified and extracted with EtOAc to afford Cap-5 as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 2.26-2.17 (m, 2H), 2.07-1.95 (m, 2H), 1.94-1.83 (m, 2H), 1.63-1.54 (m, 2H), 1.31 (s, 3H).

1. custom1 h
2. stirringThe reaction mixture was stirred at −78° C. for 1 h
3. temperaturegradually warm to −20° C. over 2 h
4. temperatureto warm to rt
5. stirringstirred at rt overnight
6. customThe reaction was quenched with satd
7. extractionNH4Cl and extracted with EtOAc
8. washthe organic phase was washed with water, brine
9. dry with materialdried (Na2SO4)
10. customEvaporation of the solvent

ORD record

ord-65772a82739645b2a108a2055ef79503

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09326973B2