Abstract
A concise and efficient synthesis of Gabapentin was achieved with an overall yield of 56% by 6 N HCl mediated hydrolysis of the corresponding g-lactam (6 ), obtained from the intramolecular C-CH insertion reaction of N -ter t-butyl-N -cyclohexylmethyl diazoacetamide (5 ) with 0.02 mol% Rh2 (OAc)4 catalyst.
Key words
C-CH insertion - g-lactam - GABA - gabapentin
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A General Procedure for Intramolecular C-CH Insertion Reaction of Diazoacetamide: To a solution of catalyst (1 mol%) in CH2 Cl2 (10 mL) at reflux was added diazoacet-amide (5 , 72 mg, 0.3 mmol) in CH2 Cl2 (5 mL) via a syringe pump over a 2 h period. After addition of the diazoacetamide was complete, the reaction mixture was stirred for an additional 0.5 h, and then the solvent was removed under reduced pressure. Silica gel column chromatography [eluent: 20% EtOAc in petroleum ether (b.p. 60-90 °C)] afforded the C-CH insertion product 6 as a pale yellow oil. 1 H NMR (CDCl3 , 300 MHz): δ = 3.17 (s, 2 H), 2.20 (s, 2 H), 1.46-1.36 (m, 19 H). 13 C NMR (CDCl3 , 75 MHz): δ = 175.08, 68.70, 54.43, 37.42, 35.93, 28.48, 26.54, 26.38, 23.58. FT IR: 1686 (C=O) cm-1 .; MS (EI): m /z = 209 [M+ ].
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