Gabapentin → 1-{[(alpha-Chloroisobutoxy)carbonyl]aminomethyl}-Cyclohexane Acetic Acid

To a mixture containing gabapentin (1.71 g, 10 mmol) and triethylamine (3.06 mL, 22 mmol) in dichloromethane (150 mL) was added trimethylchlorosilane (1.4 mL, 11 mmol) and the resulting mixture was stirred until clear (about 20 min). A solution containing 1-chloro-2-methylpropylchloroformate (1.27 mL, 11 mmol) in dichloromethane (10 mL) was then added at 0° C. and stirred at room temperature for 60 min. The reaction mixture was washed with 10% citric acid (30 mL) and the organic layer separated. The aqueous layer was further extracted with ether (3×20 mL) and the combined organic phases were dried over MgSO4 and then concentrated in vacuo. Chromatography of the residue on silica gel, eluting with hexane:ethyl acetate (1:4) gave 2.37 g (77%) of the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.04 (d, J=6.4 Hz, 3H), 1.06 (d, J=6.4 Hz, 3H), 1.36-1.53 (m, 10H), 2.15 (m, 1H), 2.34 (s, 2H), 3.24 (m, 2H), 5.39 (t, 1H), 6.32 (d, J=5.6 Hz), 1H). MS (ESI) m/z 306.34 (M+H+).

1. additionwas then added at 0° C.
2. stirringstirred at room temperature for 60 min
3. washThe reaction mixture was washed with 10% citric acid (30 mL)
4. customthe organic layer separated
5. extractionThe aqueous layer was further extracted with ether (3×20 mL)
6. dry with materialthe combined organic phases were dried over MgSO4
7. concentrationconcentrated in vacuo
8. washChromatography of the residue on silica gel, eluting with hexane:ethyl acetate (1:4)

ORD record

ord-62af69c021a54e829dec09aa67b03ee9

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08168623B2