Chlorosuccinimide → (1S,2S)-1-[4-chloro-5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propylamine

Participants

Reaction Steps

To a solution of {(1S,2S)-1-[5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester (1.10 g, 2.11 mmol) in 10:1 v/v acetonitrile/tetrahydrofuran (20 mL) under an atmosphere of nitrogen was added N-chlorosuccinimide (352 mg, 2.64 mmol) and the mixture was refluxed for 24 hours. The reaction was concentrated in vacuo, diluted with ethyl acetate (60 mL) and washed with saturated sodium hydrogen carbonate solution. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. To a solution of the crude product in dichloromethane (20 mL) under an atmosphere of nitrogen was added trifluoroacetic acid (6 mL) and the mixture was stirred for one hour. The reaction mixture was concentrated in vacuo then basified with saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate (2×50 mL). The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give (1S,2S)-1-[4-chloro-5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propylamine which was used in the subsequent step without further purification (860 mg, 89%).

Provenance & Evidence