2927-71-1

2,4-Dichloro-5-fluoropyrimidine is Yellow to Orange Crystalline Solid

2,4-Dichloro-5-fluoropyrimidine is used in the synthesis of two glucuronic derivatives of 5-fluorouracil as neoplasm inhibitors. It is used in the synthesis of two glucuronic derivatives of 5-fluorouracil as neoplasm inhibitors.

Notclassified

The general procedure for the synthesis of 2,4-dichloro-5-fluoropyrimidine using 5-fluoropyrimidine-2,4(1H,3H)-dione as a starting material is as follows: 5-fluoropyrimidine-2,4-diol (525 kg, 1.00 mole equivalents) was mixed with phosphorus trichloride (1545 kg, 2.50 mole equivalents) under nitrogen protection and heated to about 100 °C with stirring. Subsequently, N,N-dimethylaniline (980 kg, 2.00 mole equivalents) was slowly added over a period of about 9 hours and the reaction mixture was continued to be stirred at about 100°C for no more than 4 hours. Upon completion of the reaction, the mixture was cooled to about 20°C over about 2 hours and then the reaction was quenched by slowly pouring into a mixture of water (3150 kg) and dichloromethane (1915 kg), ensuring that the temperature was controlled below 40°C. The mixture was stirred at about 20°C for at least 3 hours and then left to stratify. The aqueous phase was washed with dichloromethane (1915 kg) and the layers were separated again. The organic phase was combined and washed at least once with concentrated aqueous hydrochloric acid (525 kg), repeated if necessary, and then with 5% w/w aqueous sodium bicarbonate (2625 kg). The washed organic solution was concentrated by distillation at atmospheric pressure to about 1310 kg to give a dichloromethane solution of 2,4-dichloro-5-fluoropyrimidine with a typical concentration of about 50% w/w and a yield of about 95%. The solution can be used directly in subsequent reactions.

[1] Patent: US2015/175639, 2015, A1. Location in patent: Paragraph 0145
[2] Journal of Organic Chemistry, 2011, vol. 76, # 10, p. 4149 - 4153
[3] Patent: KR2016/69892, 2016, A. Location in patent: Paragraph 0090-0093
[4] Chemical and Pharmaceutical Bulletin, 1991, vol. 39, # 9, p. 2288 - 2300
[5] Patent: US2005/234046, 2005, A1. Location in patent: Page/Page column 64