反应详情

A solution of 3.09 g (9.27 mmol) (4R,9aR)-6-(1-(RS)-hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester in 33 mL dichloromethane was cooled to 0 deg C. and treated with 8.8 mL (12.7 g, 0.11 mol) trifluoroacetic acid. The cooling bath was removed and the volatile components were removed at a rotary evaporator. The remaining residue was purified by column chromatography on silica gel (0.032–0.063 mm) with dichloromethane:methanol:ammonia (19:1:0.1). The remaining oil was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution and extracted with dichloromethane until all product was removed from the aqueous phase. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The remaining light brown oil was purified by column chromatography on a Chiralpak-AD column with 7% ethanol/n-heptane yielding the desired compound as a light brown solid (36.5%).

1. customThe cooling bath was removed
2. customthe volatile components were removed at a rotary evaporator
3. customThe remaining residue was purified by column chromatography on silica gel (0.032–0.063 mm) with dichloromethane:methanol:ammonia (19:1:0.1)
4. customThe remaining oil was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution
5. extractionextracted with dichloromethane until all product
6. customwas removed from the aqueous phase
7. washThe combined organic layers were washed with brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. customevaporated
11. customThe remaining light brown oil was purified by column chromatography on a Chiralpak-AD column with 7% ethanol/n-heptane yielding the desired compound as a light brown solid (36.5%)