Water → 1-((Difluoromethoxy)methyl)cyclobutanecarboxylic acid

Participants

Reaction Steps

To a stirred solution of Intermediate 223A (0.263 g, 1.263 mmol) in ethanol (3.5 mL), THF (3.5 mL), and water (3 mL) was added NaOH (0.152 g, 3.79 mmol) and the reaction mixture was stirred at RT for 16 h. The reaction mixture was concentrated and the residue dissolved in water and extracted with ethyl acetate (3×15 mL) The aqueous layer was then acidified to pH 2-3 using a 1.5 N aqueous solution of HCl and extracted with EtOAc (3×15 mL). The combined organic layer was washed with water, dried over Na2SO4 and concentrated to afford Intermediate 223B as a brown oil (0.08 g, 35% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.41 (s, 1H), 6.97-6.40 (m, 1H), 4.15-3.90 (m, 2H), 2.38-2.09 (m, 2H), 2.01-1.51 (m, 4H).

Provenance & Evidence