Sodium Hydroxide → 1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4-[3-(6-methoxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A solution of methyl Cis(±)-1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4-[3-(6-methoxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate (Example 123) (105 mg, 0.204 mmol) in methanol (1 mL) was treated with a solution of sodium hydroxide (1N, 1 mL) the reaction was warmed to 30° C. for 18 hours. The temperature was increased to 60° C. for 6 hours. The solvents were evaporated, the reaction was diluted with ethyl acetate and water. The pH was adjusted to 7 with 1N HCl. The layers were separated. The aqueous phase was extracted with ethyl acetate (2×20 mL). The organic layers were combined dried over magnesium sulfate and concentrated at reduced pressure. The residue was taken up and dichloromethane and precipitated with ether in a dry ice/acetone bath. The solvent was decanted. The solid was dried under high vacuum to obtain 21 mg (20%) of an off-white solid.

Provenance & Evidence