Sodium Hydroxide → HCID 11347364, compound

Participants

Reaction Steps

A 500 mL round bottom flask was charged with ethyl 6-(1,1-difluoroethyl)-2-(trifluoromethyl)-2H-chromene-3-carboxylate from Step 1 (0.385 g, 1.145 mmole), THF: EtOH: H2O (7:2:1 volume ratio, 3 ml), and aqueous NaOH (0.55 mL, 1.374 mmole) and stirred at r.t. for two days. The reaction was concentrated in vacuo yielding a semi-solid. The semi-solid was dissolved in water washed with diethyl ether, and the resulting aqueous phase sparged with nitrogen with warming. The resulting organic solvent-free aqueous phase was acidified with concentrated HCl solution (to pH 1) yielding a gummy solid. This mixture was extracted with ethyl acetate. The combined organics were dried over MgSO4, filtered, diluted with isooctane, and concentrated in vacuo yielding an oil. Upon standing, the oil formed a white crystalline powder (0.159 g, 45%): mp 156-158° C. (w/decomp). LCMS m/z 309 (M+H). HRMS m/z 307.0408 (M−H, C13H8F5O3, Calc'd 307.0388). 1H NMR (acetone-d6/300 MHz) 12.2-11.2 (br s, ˜0.5H (1H exch), 7.97 (s, 1H), 7.72 (s, 1H), 7.61(d d, 1H, J=8.5, 2.2 Hz), 7.13 (d, 1H, J=8.7 Hz), 5.89 (q, 1H, J=7.0 Hz), 1.97 (t, 3H, J=18.3 Hz).

Provenance & Evidence