The general procedure for the synthesis of L-valine ethyl ester hydrochloride from ethanol and L-valine is as follows: 5 kg (42.7 mol) of L-valine and 4 kg of anhydrous ethanol were added to a 50-liter glass reactor and stirred until complete dissolution. After cooling the reaction mixture to 0-10°C, 8.8 liters of thionyl chloride were added slowly and dropwise. After the dropwise addition was completed, the reaction mixture was gradually heated to reflux and the reaction was maintained for 18 hours. Upon completion of the reaction, the reaction solution was concentrated to dryness. Subsequently, 15 liters of isopropyl acetate was added to the dried residue at 15 to 20°C and stirred for 1 hour. Finally, the product was collected by diafiltration to give 6.1 kg of off-white solid, Intermediate 1 (where R1 is ethyl).
[1] Tetrahedron, 2005, vol. 61, # 35, p. 8423 - 8442
[2] Journal of the Indian Chemical Society, 2001, vol. 78, # 3, p. 137 - 141
[3] Journal of the American Chemical Society, 2018, vol. 140, # 22, p. 6818 - 6822
[4] Chemistry of Natural Compounds, 1994, vol. 30, # 2, p. 238 - 244
[5] Khimiya Prirodnykh Soedinenii, 1994, # 2, p. 261 - 268
