Synthesis
The general procedure for the synthesis of N-acetyl-L-valine from L-valine and acetic anhydride was as follows: L-valine (200 g, 1.7 mol) was dissolved in distilled water (500 mL), followed by the addition of 30% sodium hydroxide solution (170 mL). After cooling the reaction mixture to 0-5°C, acetic anhydride (32 mL, 1.4 eq.) was added slowly and dropwise. This was repeated six times (total acetic anhydride: 6 x 32 mL; 30% sodium hydroxide solution: 6 x 34 mL) by alternating dropwise additions of 30% sodium hydroxide solution (34 mL) and acetic anhydride (32 mL) while maintaining the temperature at 0-5°C. After the addition was completed, the reaction mixture continued to be stirred at 0°C for 2 hours. Subsequently, 32% hydrochloric acid (380 mL) was slowly added to adjust the pH to below 3 while maintaining the reaction temperature at 0°C. The resulting slurry was allowed to crystallize for 12 h. The solid product was collected by filtration and the filter cake was washed with 0.1 N hydrochloric acid (100 mL). Finally, the wet N-acetyl-L-valine was dried to give 233 g of white crystalline solid in 86% yield.
References
[1] New Journal of Chemistry, 2002, vol. 26, # 7, p. 834 - 843
[2] Synthetic Communications, 1992, vol. 22, # 2, p. 257 - 264
[3] Patent: WO2005/40097, 2005, A1. Location in patent: Page/Page column 9
[4] Journal of the American Chemical Society, 2011, vol. 133, # 43, p. 17176 - 17179
[5] Journal of the American Chemical Society, 1956, vol. 78, p. 4636,4642
