Aluminium lithium hydride → (3S)-1-Benzyl-3-(propan-2-yl)piperazine

Participants

Reaction Conditions

Reaction Steps

LAH (1.87 g, 49.3 mmol) was suspended in 60 mL of THF with stirring and cooled to 0° C. under an inert atmosphere. (5S)-5-(1-methylethyl)-1-(phenylmethyl)-2,3-piperazinedione (2.43 g, 9.87 mmol) was dissolved in 50 mL of THF and added dropwise via addition funnel over 20 min. The funnel was rinsed with an additional 10 mL of THF. The reaction was warmed to rt and stirred for 2 days. The reaction was quenched by the careful sequential addition of 1.9 mL of H2O, 1.9 mL of 1N NaOH (aq.), and 5.7 mL of H2O. The slurry was stirred for 30 min and filtered. The solids were washed with DCM. The filtrate was concentrated in vacuo. Purification by flash chromatography afforded the title compound of step B (1.68 g, 7.69 mmol, 78%). 1H NMR (400 MHz, DMSO-d6) δ 7.33-7.18 (m, 5H), 3.40 (AB, ΔνAB=34.5 Hz, JAB=13.2 Hz, 2H), 2.78 (m, 1H), 2.71-2.51 (m, 3H), 2.28 (m, 1H), 1.88-1.72 (m, 2H), 1.63 (t, J=10.3 Hz, 1H), 1.45 (m, 1H), 0.83 (d, J=6.8 Hz, 3H), 0.79 (d, J=6.8 Hz, 3H).

Provenance & Evidence