4-Toluenesulfonyl chloride → 1-(4-Methoxy-benzoyl)-3-(toluene-4-sulfonyloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

4-Toluenesulphonyl chloride (131 g, 687 mmol) and trimethylamine hydrochloride (43.8 g, 458 mmol) were added to 3-hydroxymethyl-1-(4-methoxy-benzoyl)-pyrrolidine-3-carboxylic acid ethyl ester (140.7 g, 457.8 mmol) (see Preparation 10) and triethylamine (160 mL, 1140 mmol) in dichloromethane (1400 mL) at 0° C. The reaction mixture was stirred at 0° C. for 4 hours then at RT for 18 hours. Cooled to 0° C. and trimethylamine hydrochloride (21.9 g, 229 mmol) was added, followed by 4-toluenesulphonyl chloride (17.45 g, 91.6 mmol). The reaction mixture was stirred at 0° C. for 4 hours. Water (500 mL) was added and stirred for 10 minutes. The reaction mixture was washed with 2M citric acid aqueous solution (1400 mL) and saturated aqueous NaHCO3 (1400 mL). The organic layer was separated, washed with water (1300 mL) then concentrated under reduced pressure to afford the title compound as a brown oil (215.15 g, 100%).

Provenance & Evidence