Water → Tak-778

Participants

Reaction Conditions

Reaction Steps

A solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimidee hydrochloride (0.39 g) in dichloromethane (7 ml) was added to a solution of (2R,4S)-(−)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid (0.47 g) and diethyl 4-aminobenzylphosphonate (0.41 g) in N,N-dimethylformamide (DMF) (7 ml) at 0° C., followed by the addition of 1-hydroxybenzo-triazole (HOBt) (0.28 g). This mixture was stirred at 0° C. for 1 hour and at room temperature (25° C.) for 15 hours, after which it was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried (using MgSO4), after which the solvent was distilled off; the residual crystals were collected by filtration, followed by recrystallization from ethyl acetate-hexane and then recrystalized from methanolhexane to yield (2R,4S)-(−)-N-[4-(diethoxyphosphorylmethyl)phenyl]-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzo-thiepin-2-carboxamide (0.37 g, 44%). Colorless Prisms. Melting point 181-182° C. Optical rotation [α]D (23° C.) −187.4° (c=0.50, CHCl3).

Provenance & Evidence