Reaction #544463

Reaction equation

gabapentin

triethylamine

1-chloro-2-methylpropylchloroformate

trimethylchlorosilane

→

title compound

Yield 77.5%

[(α-Chloroisobutoxy)carbonyl]aminomethyl-1-Cyclohexane Acetic Acid

Yield 77.5%

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   workup.ADDITIONwas then added at 0° C.
2. 2
   workup.STIRRINGstirred at room temperature for 60 min
3. 3
   WashThe reaction mixture was washed with 10% citric acid (30 mL)
4. 4
   Otherthe organic layer separated
5. 5
   ExtractionThe aqueous layer was further extracted with ether (3×20 mL)
6. 6
   Dryingthe combined organic phases were dried over MgSO4
7. 7
   Concentrationconcentrated in vacuo
8. 8
   WashChromatography of the residue on silica gel, eluting with hexane:ethyl acetate (1:4)

Procedure

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+).

Source