(r)-(6-Cyano-2,3,4,9-tetrahydro-1h-carbazol-3-yl)-carbamic acid benzyl ester → (3R)-3-Amino-2,3,4,9-tetrahydro-1H-carbazole-6-carbonitrile

Participants

Reaction Steps

Combine (R)-(6-cyano-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-carbamic acid benzyl ester (Preparation 62) (7.1 mmol, 2.44 g) in anhydrous ethanol (100 mL). To the stirred solution add 5% palladium/carbon (600 mg). Purge and fill the reaction vessel with hydrogen (3×) and stir the reaction mixture under hydrogen at atmospheric pressure for about 18 h. Filter the reaction mixture through a Celite® and wash the cake with methanol. Strip the filtrate to dryness and isolate the first crop via crystallization from ethyl acetate/methanol/hexanes to yield 720 mg of pure product. Strip the crystallization mother liquors to dryness, purify and isolate additional product via flash chromatography (25% methanol/dichloromethane isocratic) for a total yield of 1.17 g (78%). LCMS 100% (m/e) 212 (M+1, APES-pos), 210 (M−1, APES-neg); 1H NMR (DMSO, 400 MHz): δ 11.29 (s, 1H), 7.81 (d, 1H, J=0.9 Hz), 7.36 (dd, 1H, J=8.4, 0.9 Hz), 7.30 (dd, 1H, J=8.4, 1.8 Hz), 3.11-3.02 (m, 1H), 2.87 (dd, 1H, J=15.4, 4.8 Hz), 2.79-2.70 (m, 2H), 2.28 (dd, 1H, J=15.4, 8.4 Hz), 1.97-1.89 (m, 1H), 1.78 (s, 2H), 1.66-1.54 (m, 1H)

Provenance & Evidence