Dimethyl Sulfoxide → methyl 3-[(3S,5R)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]acrylate

Participants

Reaction Conditions

Reaction Steps

DMSO (0.14 mL) was added to a solution of oxalyl chloride (0.16 mL) in dichloromethane (10 mL) in a nitrogen atmosphere at −78° C. over five minutes, and the reaction solution was stirred at −78° C. for five minutes. A solution of 9H-fluoren-9-ylmethyl (3S,5R)-3-hydroxymethyl-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylate (470 mg) in dichloromethane (2 mL) was added to the reaction solution at −78° C., and the reaction solution was stirred at −78° C. for 30 minutes. Triethylamine (0.86 mL) was added to the reaction solution at −78° C., and the reaction solution was stirred at −78° C. for 20 minutes. A saturated ammonium chloride solution was added to the reaction solution at −78° C., and the reaction solution was heated to room temperature. Then, dichloromethane was added to the reaction solution, and the organic layer was separated. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. Trimethyl phosphonoacetate (0.28 mL) was added to a mixed solution of sodium hydride (containing 60% mineral oil, 58 mg) in THF (10 mL)-DMF (2 mL) at 0° C., and the reaction solution was stirred at 0° C. for 30 minutes. A solution of the residue obtained above in THF (2 ml) was added to the reaction solution at 0° C., and the reaction solution was stirred at 0° C. for 30 minutes. A saturated ammonium chloride solution and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. Diethylamine (1 mL) was added to a solution of the residue in acetonitrile (4 mL), and the reaction solution was stirred for 30 minutes. Toluene was added to the reaction solution, which was then concentrated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: heptane->heptane:ethyl acetate=1:1) to obtain 227 mg of an E/Z isomer mixture of the title compound. The property values of the compound are as follows.

Provenance & Evidence