Gabapentin → Prop-2-enyl 2-[1-(aminomethyl)cyclohexyl]acetate;hydrochloride

Participants

Reaction Conditions

Reaction Steps

A dry 3 L, three-neck, round-bottomed flash fitted with a magnetic stirring bar and a 500 mL pressure-equalizing addition funnel is flushed with nitrogen gas. The flask is charged with gabapentin (171 g, 1.0 mol) and allyl alcohol (1 L, 852 g, 14.6 mol) and the entire mixture is cooled to 0° C. in an ice-water bath. Thionyl chloride (225 mL, 360 g, 3.0 mol) is added dropwise over a period of 1 h to the stirred solution. The reaction mixture is allowed to stir at room temperature for 16 h, then is diluted with ethyl ether (2 L) and cooled to 0° C. while stifling. After several minutes white crystals form, which are collected by filtration. The crude product is recrystallized from a ⅓ (v/v) mixture of ethanol and ethyl ether (2 L) to give the product as a white solid (220 g 88%). m.p.: 138-142° C. 1H NMR (CD3OD, 400 MHz): δ 1.36-1.54 (m, 10H), 2.57 (s, 2H), 3.05 (s, 2H), 4.61 (d, J=6 Hz, 2H), 5.22 (dd, J1=10.4 Hz, J2=1.2 Hz, 1H), 5.33 (dd, J1=17.2 Hz, J2=1.4 Hz, 1H), 5.90-6.00 (m, 1H). MS (ESI) m/z 212.0 (M-Cl)+.

Provenance & Evidence