Citric Acid → (R)-tert-butyl 3-(tosyloxymethyl)piperidine-1-carboxylate

Participants

Reaction Steps

To a suspension of (R)-tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate (400 mg, 1.858 mmol) and pyridine (1.10 ml, 13.60 mmol) in tetrahydrofuran (5 ml) was added p-toluenesulfonyl chloride (425 mg, 2.230 mmol) and stirred for 10 hr. To the reaction was added citric acid (4 g) and water (10 mL) and extracted with ethyl acetate (3×10 mL). The organics were combined, dried (MgSO4), filtered, and concentrated. The residue was purified by Analogix® Intelliflash280™ (SiO2, 0-40% ethyl acetate in hexanes). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.13-1.21 (m, 1H) 1.23-1.31 (m, 1H) 1.37 (s, 9H) 1.46-1.55 (m, 1H) 1.59-1.74 (m, 2H) 2.43 (s, 3H) 2.68-2.83 (m, 1H) 3.28-3.32 (m, 1H), 3.67-3.73 (m, 2H) 3.89 (d, J=6.10 Hz, 2H) 7.49 (m, 2H) 7.76-7.81 (m, 2H); MS (DCI) m/z 387 (M+NH4)+.

Provenance & Evidence