Synthesis
The general procedure for the synthesis of (S)-2-amino-N-methylpropionamide hydrochloride from L-alanine ethyl ester hydrochloride was as follows: ethyl L-alanine ethyl ester hydrochloride (8.1 g, 52.4 mmol) was dissolved in ethanol-methylamine solution (36 mL, 289 mmol), and the reaction was stirred for 97 hours. Upon completion of the reaction, the solvent was removed by evaporation. The residue was dissolved in 4 M potassium carbonate solution (30 mL) and saturated sodium bicarbonate solution (20 mL) and subsequently extracted with chloroform (5 × 25 mL). The organic phases were combined, dried over sodium carbonate and evaporated to give the crude (S)-2-amino-N-methylpropionamide as a red oil (3.62 g, 35.5 mmol, 68% yield). The free amine (1.9 g, 18.5 mmol) was dissolved in ether (200 mL) and treated by passing hydrogen chloride gas for 10 min. At the end of the reaction, the product was collected by filtration and washed with ether to afford (S)-2-amino-N-methylpropionamide hydrochloride as clarified crystals (2.2 g, 16.0 mmol, 86% yield). The product was further purified by recrystallization from ethanol and hexane; melting point 213-215 °C; [α]D25 +19.6 (c 0.1, CH3OH); νmax (NaCl disk)/cm-1 3408, 1674, 1514, 1417, 1275, 1169; δH (400 MHz, D2O) 3.85 (1H, q, J 7.1 Hz, CH), 2.60 (3H, s, NCH3), 1.32 (3H, d, J 7.1 Hz, CCH3); δC (100 MHz, D2O) 174.1 (C), 51.2 (CH), 28.5 (CH3), 19.2 (CH3).
References
[1] Tetrahedron, 2011, vol. 67, # 23, p. 4263 - 4267
