Sodium Hydroxide → 1-(difluoromethyl)cyclobutane-1-carboxylic acid

Participants

Reaction Steps

To a stirred solution of Intermediate 235A (0.24 g, 1.347 mmol) in ethanol (3.5 mL), THF (3.5 mL) was added NaOH (0.162 g, 4.04 mmol) in water (3 mL) and the reaction mixture was stirred at RT for 16 h. The reaction mixture was concentrated and the residue was diluted with water (3 mL) and extracted with ethyl acetate. The aqueous layer was then acidified to pH 3-4 using an aqueous solution of 1.5 N HCl and extracted with ethyl acetate (3×25 mL) The combined organic layer was washed with water, dried over Na2SO4, filtered and the filtrate concentrated. The residual mass was then azeotroped with toluene to afford Intermediate 235B as a brown solid (0.12 g, 59% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.33 (s, 1H), 6.55-5.94 (m, 1H), 3.28-3.03 (m, 2H), 2.41-2.10 (m, 2H), 2.00-1.68 (m, 2H).

Provenance & Evidence