Hydrochloric Acid → tert-butyl N-[(piperidin-3-yl)methyl]carbamate

Participants

Reaction Steps

A cold solution of HCl in MeOH (prepared by adding acetyl chloride (13.5 mL, 14.9 g, 0.19 mol) to 1 L of MeOH) was added to a cold solution of tert-butyl pyridin-3-ylmethylcarbamate (41.0 grams, 0.20 mol) in MeOH (100 mL). The solution was transferred to a Parr hydrogenation apparatus at 12° C. PtO2 (3 g) was added, and 12 bar pressure of H2 was applied. After 16 hours 1H NMR of a concentrated sample indicated the reaction to be complete. The catalyst was filtered, and conc. aq. NaOH (20 mL) was added to neutralize the HCl. The solution was concentrated to remove the bulk of the MeOH and extracted with tert-butyl methyl ether (4×200 mL). The combined organic layers were washed with saturated aqueous NaCl solution, dried over Na2SO4, and concentrated to give the product (40.16 g, 0.187 mol, 95%) as a yellow oil that crystallized upon standing. 1H NMR (300 MHz, CDCl3): δ 4.62 (bs. s, 1H), 3.06-2.94 (m, 4H), 2.52 (dt, J=12 Hz, 3 Hz, 1H), 2.28 (dd, J=12 Hz, 10 Hz, 1H), 1.82-1.72 (m, 1H), 1.70-1.51 (m, 3H), 1.49-1.34 (m, 1H), 1.42 (s, 9H), 1.06 (dq, J=12 Hz, 4 Hz, 1H) ppm.

Provenance & Evidence