反应详情

温度

-40 °C

Under a nitrogen atmosphere, 1-bromo-3,4,5-trifluorobenzene (2 mL) was added to a diethyl ether (200 mL) suspension of magnesium (6.87 g) and iodine (trace amount) and the resultant was heated by heatgun until reaction started. 1-bromo-3,4,5-trifluorobenzene (31.7 mL) was further added dropwise. Once reflux has stopped, stirring was continued for 1.5 hours at room temperature. Under a nitrogen atmosphere, previously prepared 3,4,5-trifluorophenyl magnesium bromide was added dropwise at −35° C. or less into a tetrahydrofuran (800 mL) solution of (S)-3-benzyloxymethyl-5-oxomorpholine-4-carboxylic acid t-butyl ester (82.8 g) that was cooled to −40° C. Stirring was continued for 2 hours at −40° C., saturated ammonium chloride aqueous solution (200 mL) and water (300 mL) were added, and the temperature was raised to room temperature. Toluene (500 mL) was added, and the organic layer was partitioned. The organic layer was washed with brine. The aqueous layers were combined, ethyl acetate (400 mL) was added, and the organic layer was partitioned. The organic layers were combined and dried over anhydrous magnesium sulfate, and the solvent was removed under a vacuum. The residue was purified with silica gel column chromatography (heptane/ethyl acetate 9/1→8/2→3/1), and the title compound was obtained (82.6 g). The physical property values are as follows.

1. temperaturethe resultant was heated by heatgun until reaction
2. temperatureOnce reflux
3. stirringStirring
4. waitwas continued for 2 hours at −40° C.
5. temperaturethe temperature was raised to room temperature
6. customthe organic layer was partitioned
7. washThe organic layer was washed with brine
8. additionethyl acetate (400 mL) was added
9. customthe organic layer was partitioned
10. dry with materialdried over anhydrous magnesium sulfate
11. customthe solvent was removed under a vacuum
12. customThe residue was purified with silica gel column chromatography (heptane/ethyl acetate 9/1→8/2→3/1)