Diethyl Ether → 1-(3-Benzoyl-thioureido)-1H-pyrrole-2-carboxylic acid ethyl ester

Participants

Reaction Steps

Chloramine was made according to J. Org. Chem., Vol 69 (4), 1368-1371. Into 4 L Erlenmyer flask, 1H-Pyrrole-2-carboxylic acid methyl ester (25.00 g, 0.1938 mol) and Tetrahydrofuran (1000 mL, 10 mol) were added and stirred at room temperature for 20 minutes under an atmosphere of Nitrogen. 1.00 M of Potassium tert-Butoxide in Tetrahydrofuran (500.0 mL, 0.5000 mol) was added and stirred for 30 minutes at room temperature. 0.15 M of Chloramine in Ether (2100 mL, 0.31 mol) was added to the reaction mixture at 10° C. over 20 minutes with nitrogen bubbling into the reaction mixture. The reaction was stirred at room temperature for 2 hours. HPLC suggested 72% conversion (18% SM remained). Saturated Na2S2O3 (500 mL) was added at 10° C. over 30 minutes. The mixture was stirred for one hour. The organic was separated, washed with water, then subsequently with Brine, and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was concentrated to approximately 500 mL. Benzoyl isothiocyanate (22.75 g, 0.1394 mol) in Tetrahydrofuran (100 mL, 1 mol) was added dropwise to the residual organic. The reaction mixture was stirred at room temperature overnight. The solvent was removed under vacuum. The solid was partitioned with Et2O (200 mL) and stirred for 30 minutes. The solid was filtered and washed with hexane/Et2O (9 to 1) to give 1-(3-Benzoyl-thioureido)-1H-pyrrole-2-carboxylic acid ethyl ester (38.20 g) as an off white solid. NMR 1H (DSMO-d6) 12.89 (s, 1H), 11.92 (s, 1H), 7.99 (d, 2H, J=7.46 Hz), 7.68 (t, 1H, J=7.37 Hz), 7.55 (t, 1H, J=7.81 Hz), 7.19 (dd, 1H, JJ=2.04, 1.64 Hz), 6.89 (dd, 1H, JJ=1.76, 1.60 Hz), 6.20 (dd, 1H, J=3.00, 1.04 Hz), 3.68 (s, 3H).

Provenance & Evidence