(R)-tert-butyl 3-(2-(2-ethylphenoxy)benzoyl)piperidine-1-carboxylate → (R)-tert-butyl 3-((S)-1-(2-(2-ethylphenoxy)phenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate

Participants

Reaction Steps

To a solution of (R)-tert-butyl 3-(2-(2-ethylphenoxy)benzoyl)piperidine-1-carboxylate (2.25 g, 4.09 mmol) in THF (7 mL) at −20° C., 4-methoxybutylmagnesium chloride in THF (1.63 M, 5.0 mL, 8.15 mmol) was added dropwise. The resulting solution was warmed to rt slowly, and the completion of reaction was confirmed by LC-MS (˜20 min). The reaction was quenched with satd aq NH4Cl (8 mL) and extracted with ether (4×10 mL). The combined organic layers were washed with water and brine, and solvent was removed under vacuum to give a crude product, which was purified by flash column chromatography to give (R)-tert-butyl 3-((S)-1-(2-(2-ethylphenoxy)phenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate (1.52 g, 75%). 1H NMR (CDCl3, 400 MHz) δ: 7.52 (d, 1H), 7.26 (dd, 1H), 7.20-7.00 (m, 4H), 6.78 (d, 1H), 6.60 (d, 1H), 4.34 (d, 1H), 4.00 (d, 1H), 3.30 (t, 2H), 3.24 (s, 3H), 2.78 (dd, 1H), 2.64 (q, 2H), 2.62 (m, 1H), 2.40 (m, 1H), 2.26 (m, 1H), 1.92 (m, 1H), 1.56 (m, 4H), 1.40 (s, 9H), 1.30 (m, 3H), 1.22 (t, 3H); MS m/z 520 (M+Na+).

Provenance & Evidence