反应详情

温度

-78 °C

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.

1. stirringthe reaction solution was stirred at −78° C. for 30 minutes
2. stirringthe reaction solution was stirred at −78° C. for 20 minutes
3. temperaturethe reaction solution was heated to room temperature
4. customthe organic layer was separated
5. dry with materialThe resulting organic layer was dried over magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. additionTrimethyl 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.
8. stirringthe reaction solution was stirred at 0° C. for 30 minutes
9. customA solution of the residue obtained above in THF (2 ml)
10. additionwas added to the reaction solution at 0° C.
11. stirringthe reaction solution was stirred at 0° C. for 30 minutes
12. customthe organic layer was separated
13. dry with materialThe resulting organic layer was dried over magnesium sulfate
14. concentrationconcentrated under reduced pressure
15. additionDiethylamine (1 mL) was added to a solution of the residue in acetonitrile (4 mL)
16. stirringthe reaction solution was stirred for 30 minutes
17. additionToluene was added to the reaction solution, which
18. concentrationwas then concentrated under reduced pressure
19. customThe residue was purified by silica gel chromatography (elution solvent: heptane->heptane:ethyl acetate=1:1)
20. customto obtain