perfluorophenyl 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate → perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate

Participants

Reaction Steps

A round bottom flask was charged with perfluorophenyl 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (see EXAMPLE 46, STEP 1) (391 mg, 0.647 mmol), dicyanozinc (380 mg, 3.24 mmol), and palladum (0) bis(tri-tert-butylphosphine) (33.1 mg, 0.065 mmol). The flask was flushed with Ar (g), then DMAC (3235 μL) was added. A reflux condenser was attached, and the flask was lowered into a 60° C. heating bath overnight. The mixture was cooled to room temperature and diluted with water and EtOAc. A small portion of brine was added to break up an emulsion, and the layers were separated. The aq. layer was extracted with EtOAc (2×), and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The product was purified by chromatography on silica gel (40 g, 0 to 30% EtOAc/Heptane) to give perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (327 mg, 0.594 mmol) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.50 (d, J=2.2 Hz, 1 H), 8.26-8.13 (m, 1 H), 7.85 (d, J=8.5 Hz, 1 H), 7.43 (d, J=2.2 Hz, 1 H), 7.33 (dd, J=2.3, 8.8 Hz, 1 H), 6.80 (d, J=8.8 Hz, 1 H), 4.45-4.40 (m, 2 H), 3.94 (t, J=4.2 Hz, 2 H). m/z (ESI) 573.2 (M+H)+.

Provenance & Evidence