HCID 86680515, compound → (7R,8aS)-7-Hydroxyhexahydropyrrolo[1,2-a]pyrazin-1(2H)-one

Participants

Reaction Conditions

Reaction Steps

(2S,4R)-Methyl 1-(cyanomethyl)-4-hydroxypyrrolidine-2-carboxylate (0.5 g, 2.71 mmol) from Step 1 and methanol (20 mL) were added to Raney®-nickel 2800 water slurry (1.000 g, 17.04 mmol) in a 50 mL pressure bottle. The reaction mixture was stirred for 9 hours under hydrogen (30 psi) at 80° C. The mixture was filtered though a nylon membrane, and the solvent was evaporated in vacuo. The resulting crude oil was purified on a 4 g silica gel cartridge eluted with 20% methanol/dichloromethane over 10 minutes to provide the crude solid product. Further purification on a 4 g cartridge with 20% methanol (2 N ammonia)/dichloromethane afforded (7R,8aS)-7-hydroxy-hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one (0.204 g, 1.303 mmol, 48% yield) as a white solid. 1H NMR (500 MHz, pyridine-d5) δ ppm 8.44 (bs, 1H), 6.57 (d, J=4.0 Hz, 1H), 4.68 (d, J=3.2 Hz, 1H), 3.86 (t, J=8.2 Hz, 1H), 3.54-3.45 (m, 1H), 3.30 (dd, J=10.0, 5.8 Hz, 1H), 3.28-3.23 (m, 1H), 2.95 (dd, J=9.9, 3.6 Hz, 1H), 2.88 (dt, J=12.0, 4.2 Hz, 1H), 2.79 (ddd, J=12.1, 9.4, 4.2 Hz, 1H), 2.61-2.55 (m, 2H); MS (ESI+) m/z 157 (M+H)+.

Provenance & Evidence