Water → (R)-tert-butyl 4-((5-(benzyloxy)hexyl)oxy)-4-methylpiperidine-1-carboxylate

Participants

Reaction Steps

To a solution of (R)-tert-butyl 4-((5-hydroxyhexyl)oxy)-4-methylpiperidine-1-carboxylate (4.5 g, 14.27 mmol) in DMF (50 mL) at 0° C. was added 60% NaH (0.685 g, 17.12 mmol) and the resulting mixture was stirred at room temp for 1 h. Benzyl bromide (2.55 mL, 21.40 mmol) was then added and the mixture was stirred for 16 h. Water (20 mL) was then added and the mixture was extracted with ether (100 mL), washed with brine (25 ml), dried (Na2SO4), filtered and concentrated. The residue was then purified by Biotage (0-20% EtOAc/hexane) to afford (R)-tert-butyl 4-((5-(benzyloxy)hexyl)oxy)-4-methylpiperidine-1-carboxylate (3.5 g, 8.63 mmol, 60.5% yield) as light yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.38-7.35 (m, 4H), 7.31-7.25 (m, 1H), 4.60 (d, J=11.8 Hz, 1H), 4.48 (d, J=11.8 Hz, 1H), 3.86-3.62 (m, 3H), 3.58-3.50 (m, 1H), 3.31 (t, J=6.3 Hz, 2H), 3.14 (br. s., 2H), 1.74 (d, J=12.9 Hz, 2H), 1.59-1.51 (m, 3H), 1.47 (s, 9H), 1.46-1.37 (m, 4H), 1.22 (d, J=6.1 Hz, 3H), 1.17 (s, 3H). LCMS (M+H)=406.3.

Provenance & Evidence