Nitrogen → 4-(4-Fluoro-benzylcarbamoyl)-benzenesulfonyl chloride

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Reaction Steps

Add 4-chlorosulfonyl-benzoyl chloride (103 g (0.433 mol) and anhydrous THF (1.2 L) to a 5-L 3-neck round bottom equipped with overhead stirrer, dropping funnel, N2 line, and temperature probe and cool to −78° C. Add to the stirring solution dropwise over 4 h a solution of 4-fluorobenzylamine (52 g, 0.416 mol), triethylamine (42 g, 0.415 mol), and 4-DMAP (5.3 g, 0.043 mol) in dry THF (1.2 L). Slowly bring to room temperature the resulting mixture and stir overnight. Filter the solids, back-wash with THF, and concentrate the filtrate to a solid. Partion the solid between 1N HCl (1 L) and ethyl acetate (2×1 L). Combine the organics, dry over magnesium sulfate, filter, and concentrate to a solid. Suspend the solid in methyl t-butyl ether (1 L), stir at room temperature for 2 h, filter, and back-wash with ethyl ether (500 mL). Dry the resulting white powder (20 mm Hg, 40° C.) to give 4-(4-fluoro-benzylcarbamoyl)-benzenesulfonyl chloride as a white solid (108.5 g, 80%): 1HNMR (DMSO-d6) δ 9.07 (t, J=5.9 Hz, 1H), 7.82 (d, J=8.3 Hz, 2H), 7.65 (d, J=7.8 Hz, 2H), 7.35 (m, 2H), 7.14 (t, J=8.8 Hz, 2H), 4.44 (d, J=5.9 Hz, 2H); MS (ESI) m/z 326 (m−H); HPLC, 93.6%.

Provenance & Evidence