Isopropyl chloroformate → Isopropyl 4-Hydroxypiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A magnetically stirred solution of 4-hydroxypiperidine (70.3 g, 695 mmol) and N,N-diisopropylethylamine (105 mL, 600 mmol) in dichloromethane (1.0 L) was cooled to 10° C. under N2. A solution of isopropyl chloroformate (1.0 M in toluene, 580 mL, 580 mmol) was added dropwise over 2 h, maintaining a temperature of 10-15° C. The reaction mixture was stirred for an additional 2 h and then extracted with 1 N HCl (1.2 L). The organic extract was dried over MgSO4, and the solvent was removed under reduced pressure to give the title compound (90.3 g, 83%) as a pale, straw-colored oil. Exact Mass calculated for C9H17NO3: 187.1. Found: LCMS m/z=188.2 (M+H+), 210.3 (M+Na+); 1H NMR (400 MHz, CDCl3) δ 1.24 (d, J=6.3 Hz, 6H), 1.47 (m, 2H), 1.86 (m, 2H), 3.08 (m, 2H), 3.86 (m, 3H), 4.90 (m, 1H).

Provenance & Evidence