m-Bromobenzenesulphonyl chloride → (S)-tert-butyl 4-(3-bromophenylsulfonyl)-3-methylpiperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

3-bromobenzene-1-sulfonyl chloride and (S)-tert-butyl 3-methylpiperazine-1-carboxylate was coupled following as follows: Dissolve 1 g (5 mmol) of the amine in 10 mL of methylene chloride. Add 2.0 eq. of diisopropyl ethylamine. Cool to 0° C. and add 1.5 equivalents of bromobenzene sulfonyl chloride dropwise (ca. 1 min) and stir for 5 min. Warm to rt and stir for an additional 16 h. Work up by adding a saturated solution of NaHCO3 and extracting with EtOAc. Wash the organic layer with HCl (1 N) followed by NaHCO3 and brine. Remove the solvent to afford crude, yellow oil. Purification of the sulfonamide derivative by Biotage on silica gel (99% MeOH/DCM) affords the desired product as a yellow oil. The yield was 55%. LC-MS showed the product was >95% pure and had the expected M+H+ of 420. 1H NMR (Varian 300 MHz, CDCl3, shifts relative to the solvent peak at 7.24 ppm) δ 7.9 (d, 1H) 7.72-7.65 (m, 2H) 7.4 (t, 1H), 3.7 (m, 2H) 3.6 (m, 1H), 3.13-3.0 (m, 2H) 2.92-2.77 (m, 2H), 1.4 (s, 12H) 1.0 (d, 3H).

Provenance & Evidence