Ammonium Chloride → N-(2,4-dimethoxybenzyl)-3,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide

Participants

Reaction Steps

To a cold (−78° C.) solution of N-(2,4-dimethoxybenzyl)pyrimidin-2-amine (1.85 g, 7.54 mmol) in tetrahydrofuran (20 mL) was added lithium bis(trimethylsilyl)amide (1 M solution in tetrahydrofuran, 8.3 mL, 8.3 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. The mixture was cooled to −78° C. and a solution of 3,4-difluorobenzene-1-sulfonyl chloride (1.1 mL, 8.3 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. Saturated aqueous ammonium chloride (10 mL) was added, followed by with ethyl acetate (100 mL), causing a precipitate to be deposited. The solid was collected by vacuum filtration to afford N-(2,4-dimethoxybenzyl)-3,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide as a colorless solid in 73% yield (2.32 g): 1H NMR (300 MHz, CDCl3) δ8.50 (d, J=4.8 Hz, 2H), 7.74-7.60 (m, 2H), 7.16-7.06 (m, 2H), 6.94 (t, J=4.8 Hz, 1H), 6.39 (dd, J=8.3, 2.2 Hz, 1H), 6.28 (d, J=2.1 Hz, 1H), 5.41 (s, 2H), 3.76 (s, 3H), 3.45 (s, 3H); 19F NMR (282 MHz, CDCl3) δ−129.9 (d, J=20.7 Hz, 1F), −135.4 (d, J=20.7 Hz, 1F).

Provenance & Evidence