Isopropyl chloroformate → propan-2-yl N-[(2S)-7-bromo-1H,2H,3H,4H-cyclopenta[b]indol-2-yl]carbamate

Participants

Reaction Conditions

Reaction Steps

(S)-7-Bromo-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-ylamine(R)-2-hydroxy-3-phenylpropionic acid salt (60.00 g, 143.78 mmol) and diisopropylethylamine (50 mL, 296.12 mmol) are combined in toluene (165 mL). The reaction vessel is purged with nitrogen three times. The mixture is cooled to 0° C. with stirring and is held at that temperature for 30 min. A solution of isopropyl chloroformate (20.00 g, 163.20 mmol) in toluene (165 mL) is added at 0-5° C. over 10 min. The mixture is stirred at 5° C. for 10 min. HPLC shows 98.6% complete. The reaction is quenched with water (1 L) and ethyl acetate (480 mL). The mixture is filtered and the solid is washed with ethyl acetate (2×240 mL). The combined organic layer is washed with brine twice, dried (MgSO4), and filtered. The organic solvent is reduced to 50 mL. The mixture is cooled to 25° C. and tert-butyl methyl ether (50 mL) and ethyl acetate (50 mL) are added. An off-white solid is precipitated. The solid is filtered and washed with heptanes (100 mL). The solid is dried under vacuum at 50° C. for 4 h to give 44.4 g (90.3%) of a light brown solid.

Provenance & Evidence