Sodium Hydroxide → 3-(difluoromethyl)cyclobutane-1-carboxylic acid

Participants

Reaction Steps

To a stirred solution of Intermediate 252A (0.2 g, 1.122 mmol) in THF (5 mL) was added NaOH (0.112 g, 2.81 mmol) in water (2 mL) at RT. After 16 h, THF was removed under a reduced pressure and the pH of aqueous solution was adjusted to 3 using a 1.0 N aq. solution of HCl and extracted with ethyl acetate (3×10 mL). The combined organic layer was washed with water, brine, dried over Na2SO4, filtered and the filtrate concentrated to afford Intermediate 252B as yellow liquid (0.12 g, 71%, mixture of cis and trans isomers). The crude product was used in a subsequent reaction without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.01-12.22 (m, 1H), 5.84-6.32 (m, 1H), 2.97-3.13 (m, 1H), 2.59-2.77 (m, 1H), 2.06-2.32 (m, 4H).

Provenance & Evidence