Synthesis
1,3-Dimethylbarbituric acid (compound SM1) (7 kg, 44.9 mmol) was used as raw material and dissolved in 120 kg of phosphoryl chloride (POCl3). Water (2.2 kg, 122 mol) was slowly added dropwise to the above solution. After the dropwise addition, the reaction was slowly heated to reflux and maintained for 6 hours; the reaction process was monitored by high performance liquid chromatography (HPLC). Upon completion of the reaction, the reaction solution was slowly poured into a large volume of ice water (100 L) and subsequently extracted twice with dichloromethane (50 L) to combine the organic phases. The organic phase was washed with saturated brine (20 L), dried over anhydrous sodium sulfate, filtered and concentrated the organic phase, and finally the yellow solid product 6-chloro-1,3-dimethyluracil (compound SM2) (7.2 kg) was obtained by vacuum drying in 92.3% yield.
References
[1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1987, vol. 23, # 6, p. 690 - 697
[2] Khimiya Geterotsiklicheskikh Soedinenii, 1987, vol. 23, # 6, p. 836 - 844
[3] Patent: CN103755705, 2017, B. Location in patent: Paragraph 0033; 0034; 0035
[4] Justus Liebigs Annalen der Chemie, 1958, vol. 612, p. 158,162
[5] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1995, vol. 34, # 10, p. 869 - 871