反应详情

To racemic Intermediate 24, one enantiomer being (1S,2S)-1-(3,5-bis-trifluoromethyl-benzyloxymethyl)-2-phenyl-3-aza-bicyclo[3.1.0]hexane (0.08 g, 0.18 mmol) in DME (1.0 mL) was added 5-dimethylaminomethyl-1H-[1,2,3]triazole-4-carbaldehyde (˜50% pure, 0.14 g, 0.91 mmol) and the mixture stirred at room temperature for 3 hours. To the reaction flask was added sodium triacetoxyborohydride (0.08 g, 0.36 mmol) and stirring was continued for 16 hours. To the reaction flask was added 1 N HCl (2 mL) and the mixture stirred for 2 hours. 1 N NaOH solution was added cautiously and then saturated sodium bicarbonate solution was added until the pH=8. The reaction mixture was extracted with methylene chloride, the organics washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography using elution of a gradient of 50% EtOAc/Hexanes to 3% MeOH/EtOAc to give the title compound. (0.065 g, 66% yield).

1. stirringstirring
2. waitwas continued for 16 hours
3. stirringthe mixture stirred for 2 hours
4. extractionThe reaction mixture was extracted with methylene chloride
5. washthe organics washed with brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified by flash chromatography
10. washelution of a gradient of 50% EtOAc/Hexanes to 3% MeOH/EtOAc