Dimethylformamide → (R/S)-(2-Cyclohexyl-2-hydroxy-2-phenyl-acetoxymethyl)-1-(isoxazol-3-yl carbamoylmethyl)-1-methyl-pyrrolidinium bromide

Participants

Reaction Steps

To a solution comprising (1R/S,2R)-2-hydroxymethyl-1-(isoxazol-3-ylcarbamoylmethyl)-1-methyl-pyrrolidinium bromide (Intermediate B) (0.230 g, 0.718 mmol) in DMF (2 ml) is added sodium hydride (0.057 g, of a 60% dispersion in oil, 1.44 mmol) in one portion. The suspension is stirred at room temperature for 2 hours. Meanwhile, in a second reaction vessel, a solution of cyclohexyl-hydroxy-phenyl-acetic acid (0.160 g, 0.68 mmol) in DMF (2 ml) is treated with CDI (0.11 g, 0.68 mmol) in one portion. The reaction mixture is stirred at room temperature for 2 hours. The resulting CDI intermediate is added to the reaction vessel containing the sodium salt of (1R/S,2R)-2-hydroxymethyl-1-(isoxazol-3-ylcarbamoylmethyl)-1-methyl-pyrrolidinium bromide and the reaction mixture is stirred at room temperature for 2.5 hours. The reaction mixture is diluted with water (2 ml) and 0.13 ml of HBr (48% solution in water) and purified using C-18 reverse phase column chromatography (eluent-water:acetonitrile from 0% to 100% acetonitrile) to yield the titled compound.

Provenance & Evidence