Acetic Acid → methyl (7R)-7-[[(3S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl](methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

Participants

Reaction Steps

AcOH (4 eq) was added to a stirred mixture of tert-butyl 3-oxopyrrolidine-1-carboxylate (1.5 eq) and methyl (7R)-7-amino-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (1 eq, prepared as described in Example 1, Step 4) in dry DCE (1M); after 30 min Na(OAc)3BH (1.8 eq) was added and the mixture was stirred at RT for 4 h. Evaporation to dryness gave a residue that was taken in EtOAc, washed with sat. aq. NaHCO3 and brine, dried and concentrated in vacuo. AcOH (4 eq) was added to a stirred mixture of foregoing crude (1 eq) and a 37% solution of HCHO in H2O (2 eq) in dry MeOH (1M); NaCNBH3 (1.6 eq) was added and the mixture was stirred at RT for 3 h. Evaporation to dryness gave a residue that was taken in EtOAc, washed with sat. aq. NaHCO3 and brine, then dried and concentrated in vacuo. The crude material was purified by FC (Biotage, PE:EtOAc:toluene, 4:3:3) to afford methyl (7R)-7-[[(3S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl](methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (43%) and its diastereoisomer methyl (7R)-7-[[(3R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl](methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (43%). (ES+) m/z 588 (M+H)+.

Provenance & Evidence