Triethylamine → (2S,3S,5R)-4-[4-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)butanoyloxymethyl]-2-(3,5-difluorophenyl)-3,5-dimethyl-2-morpholinol

Participants

Reaction Steps

A solution of the free base of (2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethyl-2-morpholinol (20a (0.023 mole) (U.S. Pat. No. 5,104,870), triethylamine (0.025 mole) and acetonitrile (30 mL) is stirred with cooling on an ice bath. A solution of chloromethyl 4-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)butanoate (315) (0.025 mole) in acetonitrile (30 mL) is added dropwise. After the addition is complete, the reaction is heated to reflux for 2 hours. The reaction is cooled, the volatiles removed by spin evaporation, and the residue partitioned between dichloromethane and 5% aqueous sodium bicarbonate. The organic layer is washed with water, and then with a saturated sodium chloride solution. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo to give crude product, which may be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent. The fractions that contain pure product may be combined and spin evaporated in vacuo to give a solid that may be recrystallized to give (2S,3S,5R)-4-[4-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)butanoyloxymethyl]-2-(3,5-difluorophenyl)-3,5-dimethyl-2-morpholinol (620). See eg., U.S. Pat. No. 5,104,870 and Sandler, et al., Organic Functional Group Preparations, p. 324 (1968).

Provenance & Evidence