反应详情

温度

80 °C

(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate (0.45 g, 1.2 mmole) and 4-(4-fluorobenzoyl)piperidine (0.73 g, 3.54 mmole) were combined in 10 mL of DMSO under nitrogen. This solution was heated to 80° C. under nitrogen for 4 hours. After completion, the reaction was cooled to room temperature and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The resulting crude oil was column chromatographed on silica gel using first methylene chloride to remove impurities and then 1% methanol/methylene chloride to elute 0.28 g of the (S)-enantiomer of the title compound. This was recrystallized from ethanol with the addition of one equivalent of fumaric acid to give 0.30 g of pale yellow solid, m.p. 229-230° C.

1. temperatureAfter completion, the reaction was cooled to room temperature
2. custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
3. washThe organic phase was washed with brine
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated in vacuum
6. customchromatographed on silica gel using first methylene chloride
7. customto remove impurities
8. wash1% methanol/methylene chloride to elute 0.28 g of the (S)-enantiomer of the title compound