Trifluoroacetic acid → (4R,9aR)-6-(1-(S)-Hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene
Reaction equation
C(OC([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH:22]([OH:24])[CH3:23])=[CH:14][CH:13]=3)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[OH:24][C@H:22]([C:15]1[N:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[CH2:11][C@H:10]1[N:18]2[C@H:19]([CH3:21])[CH2:20][NH:8][CH2:9]1)[CH3:23]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
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 (Example 38, intermediate) 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 on a rotary evaporator. The residue was chromatographed on silica gel (0.032–0.063 mm) with dichloromethane:methanol:ammonia (19:1:0.1). The remaining oil was dissolved in dichloromethane and saturated aqueous sodium bicarbonate solution and extracted until all product was extracted 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 chromatographed on a Chiralpak-AD column with 7% ethanol/n-heptane yielding the two diastereomers, the R-diastereomer being eluted first.