Synthesis
General procedure for the synthesis of 3-amino-3-methylbutanoic acid ethyl ester hydrochloride from 3-methyl-2-butenoic acid ethyl ester: 3-methyl-2-butenoic acid ethyl ester (1 g, 7.8 mmol) was dissolved in anhydrous ethanol (12 mL), cooled to -20 °C and passed through ammonia to saturation. The reaction tube was sealed and the reaction was carried out at 90 °C for 24 hours. Upon completion of the reaction, the reaction was cooled to room temperature and nitrogen was passed through to remove residual ammonia, followed by the addition of a dioxane solution (1.9 mL) in 4N HCl. After stirring for 30 min, the reaction mixture was concentrated under reduced pressure to afford ethyl 3-amino-3-methylbutyrate hydrochloride as a gray solid (1.19 g, 84% yield).1H NMR (CDCl3, 400 MHz) δ ppm: 1.2 (t, 3H), 1.26 (s, 6H), 2.65 (s, 2H), 4.1 (q, 2H), 8.27 (br s, 3H).
References
[1] Journal of Medicinal Chemistry, 2009, vol. 52, # 2, p. 293 - 307
[2] Patent: WO2005/13986, 2005, A1. Location in patent: Page/Page column 36
[3] Patent: WO2005/14572, 2005, A1. Location in patent: Page/Page column 26; 27
[4] Patent: US2007/142414, 2007, A1. Location in patent: Page/Page column 17
[5] Patent: WO2008/20206, 2008, A2. Location in patent: Page/Page column 50
