(7R,8aS)-2-benzyl-7-hydroxyhexahydropyrrolo[1,2-a]pyrazine-1,4-dione → (7R,8aS)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol

Participants

Reaction Conditions

Reaction Steps

To a suspension of Example 19C (60 g, 0.23 mol, 1 equivalent) in tetrahydrofuran (900 mL), lithium aluminum hydride (2 M in tetrahydrofuran, 460 mL, 0.92 mol, 4 equivalents) was added slowly at about 15° C. Then, the mixture was stirred at about 65° C. for 78 hours. The reaction mixture was cooled to 0-5° C., quenched using ethyl acetate (300 mL), water (60 mL), 10% NaOH solution (60 mL), followed by water (60 mL), and the mixture was stirred at 20-25° C. for 30 minutes. The suspension was filtered through diatomaceous earth, and the filtrate was concentrated. This crude material was purified by column chromatography on silica gel using a gradient of 0-10% methanol-ethyl acetate to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.46-1.49 (m, 2H), 1.68, (t, 1H, J=9.9 Hz), 1.91 (dd, 1H, J=5.4 Hz, J=8.9 Hz), 2.04-2.13 (m, 1H), 2.15-2.49 (m, 2H), 2.67 (d, 1H, J=10.3 Hz), 2.78 (d, 2H, J=5.4 Hz), 3.25 (dd, 1H, J=4.5 Hz, J=8.9 Hz), 3.47 (dd, 2H, J=4.5 Hz, J=17.4 Hz), 4.15-4.22 (m, 1H), 4.73 (bs, 1H), 7.23-7.318 (m, 5H); 13C NMR (75 MHz, DMSO-d6) δ ppm 39.74, 51.34, 52.64, 57.61, 60.72, 62.56, 63.16, 68.46, 127.26, 128.54, 129.2, 138.84; MS (ESI) m/z 233 (M+H)+.

Provenance & Evidence