Hydrazine, ethyl-, ethanedioate (1:1) → 4-(5-benzyl-1-ethyl-(1H-pyrazol-3-yl))-1-t-butoxycarbonylpiperidine

Participants

Reaction Steps

1-(1-(t-Butoxycarbonyl)piperidin-4-yl)-4-phenyl-butane-1,3-dione (from Step A, either Method A or Method B), (0.851 g, 2.46 mmol) in methanol (25 mL) was added over 10 min to a suspension of ethylhydrazine oxalate (0.444 g, 2.96 mmol) in methanol (5 mL) in a 60° C. oil bath. After 15 h, the reaction was concentrated in vacuo and the residue was purified by repeated FC using a gradient of 50-100% ethyl acetate in hexanes to give first 4-(5-benzyl-1-ethyl-(1H-pyrazol-3-yl))-1-(t-butoxycarbonyl)piperidine as the higher Rf product isomer and then the title compound as the lower Rf. 1H NMR (500 MHz): δ 7.26˜7.31 (m, 4H), 7.19˜7.23 (m, 1H), 5.72 (s, 1H), 4.16˜4.24 (m, 2H), 4.08 (q, J=7.3 Hz, 2H), 3.94 (s, 2H), 2.76˜2.82 (m, 2H), 2.66 (tt, J=3.6 & 11.9 Hz, 1H), 1.80˜1.85 (m, 2H), 1.49˜1.58 (m, 2H), 1.48 (s, 9H), 1.45 (t, J=7.3 Hz, 3H); ESI-MS 370.2 (M+H), HPLC A: 3.70 min. The other isomer's ESI-MS 370.2 (M+H), HPLC A: 3.77 min.

Provenance & Evidence