反应详情

温度

60 °C

0.85 g (2.08 mmole) of {(2R)-8-hydroxy-7-[(methoxycarbonyl)amino]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate and 1.13 g (5.70 mmole) of 3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole were combined in DMSO (40 mL) and heated at 60° C. under nitrogen for 6 hours. After completion, the reaction was cooled to room temperature and partitioned between 300 mL each of ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuum to a viscous oil. The crude oil was dissolved in methylene chloride and was heated at reflux in the presence of carbonyl diimidazole (1.02 g) for 4 hours. The reaction was allowed to cool to room temperature and the solvent was removed in vacuum. The residue was column chromatographed on silica gel using first 20% hexane/methylene chloride, then methylene chloride and finally 2% methanol/methylene chloride as eluant. The product fractions were combined and concentrated in vacuum to give 0.080 g of the (S)-enantiomer of the title compound as a light yellow solid, m.p. 202° C.

1. temperatureAfter completion, the reaction was cooled to room temperature
2. custompartitioned between 300 mL each of ethyl acetate and saturated aqueous sodium bicarbonate
3. washThe organic phase was washed with brine
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuum to a viscous oil
7. dissolutionThe crude oil was dissolved in methylene chloride
8. temperaturewas heated
9. temperatureat reflux in the presence of carbonyl diimidazole (1.02 g) for 4 hours
10. temperatureto cool to room temperature
11. customthe solvent was removed in vacuum
12. customchromatographed on silica gel using first 20% hexane/methylene chloride
13. concentrationconcentrated in vacuum