1-Hydroxybenzotriazole → (2S,4R)-(+)-N-[4-(diethoxyphosphorylmethyl)phenyl]-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.69 g) in dichloromethane (12 ml) was added to a solution of (2S,4R)-(+)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid (0.84 g) and diethyl 4-aminobenzylphosphonate (0.73 g) in N,N-dimethylformamide (DMF) (12 ml) at 0° C., followed by the addition of 1-hydroxybenzotriazole (HOBt) (0.51 g). This mixture was stirred at 0° C. for 1 hour and at room temperature 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 (MgSO4), after which the solvent was distilled off; the residual crystals were collected by filtration, followed by recrystallization from ethyl acetate-hexane and successively from methanol-hexane to yield (2S,4R)-(+)-N-[4-(diethoxyphosphorylmethyl)phenyl]-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide (0.62 g, 41%). Colorless prisms. Melting point 183-184° C. Optical rotation [α](23° C.) +190.5° (c=0.50, CHCl3).

Provenance & Evidence