4,4-Difluoro-1-methylcyclohexane-1-carboxylic acid synthesis

Yield:1389313-41-0 77%

Reaction Conditions:

with water;sodium hydroxide in tetrahydrofuran;methanol at 70; for 0.5 h;

Steps:

4,4-Difluoro- 1 -methylcyclohexanecarboxylic acid

To a solution of ethyl 4,4-difluoro-1-methylcyclohexanecarboxylate (100 mg, 0.48 mmol) in tetrahydrofuran (2 mL), methanol (0.2 mL) and water (0.2 mL) was added sodium hydroxide(39 mg, 0.9 7mmol). The mixture was stirred at 70°C for 0.5 h. The reaction mixture was quenched by addition water 20 mL, and then added 1 mol/L aqueous solution of hydrochloric acid until pH=4 and extracted with ethyl acetate (2 x 30 mL). The combined organic phases were washed with brine (20 mL) and dried over anhydrous sodium sulfate. After filtration and concentration, the product (67 mg, 77% yield) was obtained as yellow solid. 1H NMR(ODd3, 400 MHz) 1.30 (5, 3H), 1.53-1.61 (m, 2H), 1.82-2.04 (m, 4H), 2.18-2.22 (m,2H).

References:

WO2018/211275,2018,A1 Location in patent:Page/Page column 287