反应详情

温度

0 °C

To a round bottom flask was added methylene chloride (8 mL), triethylamine (0.87 mL, 6.3 mmol), and [(SR)-1-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-methyl-amine (0.49 g, 1.6 mmol. The mixture was cooled to 0° C. and triphosgene (0.18 g, 0.61 mmol) in methylene chloride (3 mL) was added dropwise. The clear solution was stirred for 16 hours at room temperature. To the reaction mixture was added racemic Intermediate 48, one enantiomer being ((1S,2S)-2-phenyl-3-aza-bicyclo[3.1.0]hex-1-yl)-carbamic acid tert-butyl ester (0.40 g, 1.5 mmol), diisopropyl ethyl amine (0.25 mL, 1.5 mmol), and acetonitrile (8 mL). The reaction was heated to remove the methylene chloride and then refluxed for 2 hours. The solvent was removed at reduced pressure and the residue was partitioned between saturated citric acid solution and methylene chloride. The organic phase was washed with saturated sodium bicarbonate solution, brine, dried over sodium sulfate, filtered, and concentrated to give the title compounds as a foam (0.84 g, quantitative yield).

1. temperatureThe reaction was heated
2. customto remove the methylene chloride
3. temperaturerefluxed for 2 hours
4. customThe solvent was removed at reduced pressure
5. customthe residue was partitioned between saturated citric acid solution and methylene chloride
6. washThe organic phase was washed with saturated sodium bicarbonate solution, brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated