Yield:17013-01-3 360.4 g

Reaction Conditions:

with sodium tungstate;dihydrogen peroxide;sodium hydroxide in water; pH=> 4 - 14 at 63 - 80; for 5 h;

Steps:

1
j0157] In the three-necked flask, the motor stirrer, thermometer and condenser pipe are provided respectively. Trans-butenedioic acid (174 g, 1.5 mol) and 450 ml of distilled water are added. And then a solution of NaOH (90 g, 2.25 mol) and 150 ml of water is added. The neutralization reaction raises the system temperature up to 70° C. Na2WO4 (49.5 g, 0.15 mol) and 30% H202 (204 ml, 1.8 mol) are added while the reaction system is hot, and the system temperature is maintained at 63-65° C. for about 20 minutes until the heat release is complete, and the system temperature tends to be stable. The pH is maintained at >4 during this period. The reaction is carried out at 63-65° C. for 3 hours, and the temperature is raised up to 75-80° C. for 1 hout The condenser pipe is replaced with a constant pressure dropping flannel, and NaOH solution is added dropwise (20 g NaOH is dissolved in 100 ml of water). pH value is adjusted to 13-14, and starch-KI test paper appears no color, and the reaction is kept at 75-80° C. for 1 hour. Stop heating and concentrate under reduced pressure at 65° C. to a volume of 100 ml, and massive white viscous materials is precipitated. 500 ml of acetone is added, and the reaction is mechanically agitated for 1 hour and standing overnight. The reaction is suction filtered the next day, and the filter cake is washed twice with acetone and dried, yielding 360.4 g sodium salt.

References:

Institute of Pharmacology and Toxicology Academy of Military Medical Sciences P.L.A. China;LI, Song;XIAO, Junhai;ZHANG, Xian;ZHONG, Wu;ZHENG, Zhibing;WANG, Lili;XIE, Yunde;LI, Xingzhou;ZHOU, Xinbo;WANG, Xiaokui US2016/115160, 2016, A1 Location in patent:Paragraph 0157