4-Chlorobenzenesulfonyl chloride → 3-[[(1,1-Dimethylethoxy)carbonyl]amino]propyl 4-chlorobenzenesulfonate

Participants

Reaction Conditions

Reaction Steps

The reaction was analysed by TLC (3:1 ethyl acetate: isohexane, potassium permanganate stain). The reaction mixture was cooled to 22° C., and triethylamine (27 mL, 193.71 mmol) was added. After further cooling of the reaction mixture to −10° C., trimethylamine hydrochloride (6.45 g, 66.14 mmol) was added and the temperature reduced to −15° C. Stirring was continued at −15° C. for 5 minutes. A solution of 4-chlorobenzenesulfonyl chloride (27.55 g, 130.53 mmol) in DCM (127 mL) was then added over 45 minutes maintaining the temperature at less than −10° C. Once addition was complete, the reaction was stirred at −10° C. for a further 5 minutes before being warmed to 5° C. over 30 minutes. Water (196 mL) was added and the resulting biphasic mixture stirred rapidly for 5 minutes. The phases were then separated and the upper (aqueous) layer discarded. Solvent (186 mL) was removed by distillation under vacuum, keeping the temperature below 40° C. Propan-2-ol (235 mL) was then added. Further solvent (81 mL) was removed by distillation under vacuum (keeping the temperature below 40° C.), after which the mixture was cooled to 20° C. and water (88 mL) added over 60 minutes to crystallise the product from solution. The product was collected by filtration, washed with 1:1 v/v propan-2-ol: water (100 mL), suction dried as far as possible on the filter, then dried in vacuo (35° C., 16 h) to give the title compound as a white solid (14.42 g, 41.22 mmol, 32%).

Provenance & Evidence