Sodium Hydroxide → 1-Ethyl-3,3-difluorocyclobutane-1-carboxylic acid

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Reaction Steps

To a solution of Intermediate 301A (0.2 g, 0.787 mmol) in ethanol (5 mL) and water (1 mL) was added a 5N aq. solution of NaOH (0.787 mL, 3.93 mmol) and the reaction mixture was stirred at RT for 4 h. The reaction mixture was concentrated under reduced pressure and the residue was diluted with water and extracted with diethyl ether (3×5 mL). The pH of the aqueous solution was adjusted to 7.0 using a 2N aq. solution of HCl and the aqueous phase was extracted with DCM (3×10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated to afford Intermediate 301B as a pale yellow liquid (50 mg, 38.7%). 1H NMR (300 MHz, DMSO-d6) δ ppm 12.63-12.75 (m, 1H), 2.80-2.97 (m, 2H), 2.57-245 (m, 2H), 1.77 (q, J=7.55 Hz, 2H), 0.81 (t, J=7.37 Hz, 3H).

Provenance & Evidence