Triethylamine → Ethyl 4-(hydroxymethyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

4-piperidinemethanol (10.00 g, 86.8 mmol) (B1) was dissolved in dichloromethane (350 mL), cooled in an ice water bath and treated dropwise with a solution of ethyl chloroformate (9.89 g, 91.1 mmol) in dichloromethane (50 mL), followed by the dropwise addition of a solution of triethylamine (8.78 g) in dichloromethane (50 mL). The reaction was stirred at 0° C. for 15 min, then at room temperature for 10 min. The reaction was diluted with dichloromethane (250 mL) and washed successively with water (2×150 mL), 0.1 N HCl (2×150 mL), saturated brine (2×150 mL), then dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to afford ethyl 4-(hydroxymethyl)-piperidine-1-carboxylate (B2) as a viscous, pale bluish-green oil (15.60 g, 96% yield). 1H-NMR (400 MHz, CDCl3) δ 4.15 (br m, 2H), 4.09 (q, J=7.1 Hz, 2H), 3.46 (d, J=6.4 Hz, 2H), 2.72 (br t, J=12.4 Hz, 2H), 2.07 (s, 1H), 1.70 (m, 2H), 1.63 (m, 1H), 1.23 (t, J=7.2 Hz, 3H), 1.12 (m, 2H); LC/MS m/z 188.0 [M+H]+, retention time 1.56 min (RP-C18, 10-99% CH3CN/0.05% TFA).

Provenance & Evidence