N,N-bis(2-chloroethyl)-p-toluenesulphonamide → Methyl (2S)-2-{4-[(4-methylphenyl)sulfonyl]-1-piperazinyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate

Participants

Reaction Steps

A suspension of methyl (2S)-2-amino-3-(1-trityl-1H-imidazol-4-yl)propanoate (1 g, 2.4 mmol) in diisopropylethylamine (5 ml), was stirred at room temperature for 20 minutes. N,N-Bis(2-chloroethyl)-4-methylbenzenesulfonamide (720 mg, 2.4 mmol) was added and the mixture was stirred at reflux for 3 hours. The mixture was allowed to cool and diluted with acetonitrile. The resultant solution was concentrated under reduced pressure and the residue was suspended in aqueous sodium carbonate solution and extracted with dichloromethane (3×20 ml). The combined organic extracts were washed with brine (3×20 ml), dried (Na2SO4), filtered, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a solvent gradient of dichloromethane:methanol (99:1). The isolated material was dissolved in ether and the resultant solution concentrated under reduced pressure to afford the title compound as a colorless foam, 300 mg, 19% yield.

Provenance & Evidence