Synthesis
The general procedure for the synthesis of 3-amino-2,2-dimethylpropionamide from 2-cyano-2-methylpropionamide is as follows: embodiment 5 (according to the present invention) Preparation of 3-amino-2,2-dimethylpropionamide: The product of embodiment 4 was dissolved in 840 mL of methanol-ammonia mixture (containing 169 g NH3/kg), which was subsequently transferred to an autoclave. To this was added 47.9 g of Raney Ni catalyst. The reaction mixture was stirred for hydrogenation at 60-70 °C and 5 bar hydrogen pressure for 10 hours. When analysis confirmed that the feedstock was completely consumed, the reaction mixture was filtered, the filter cake was washed with methanol, and the filtrate was subsequently evaporated to give 160 g (97% yield) of crude product. The crude product was dissolved in 800 mL of isopropanol-toluene (1:9, v/v) mixed solvent for recrystallization. Finally, 124 g (78% overall yield) of the target product 3-amino-2,2-dimethylpropionamide was obtained.
References
[1] Patent: WO2012/21446, 2012, A2. Location in patent: Page/Page column 30-31
[2] Patent: WO2010/112482, 2010, A1. Location in patent: Page/Page column 29
[3] Tetrahedron Letters, 2005, vol. 46, # 37, p. 6337 - 6340
[4] Patent: WO2011/148392, 2011, A1. Location in patent: Page/Page column 64
[5] Journal of Medicinal Chemistry, 2017, vol. 60, # 3, p. 957 - 971
