反应详情

A solution of 450 g (3.49 mol) of 5-amino-2-chloropyrimidine and 790 g (6.98 mol) of triethylamine in anhydrous THF was cooled to less than 5° C. in an ice bath. To this solution was added 3,4-difluorobenzoyl chloride at a rate (2 h) that maintained the temperature of the reaction mixture below 10° C. Once the addition was complete the reaction was monitored for full conversion of the starting material to product by HPLC. Following confirmation of complete conversion, the reaction mixture was concentrated under reduced pressure. The viscous residue was dissolved in ethyl acetate (4 L) and washed with water (4 L) and 2M HCl (4 L). The organic layer was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting solid was dissolved in ethanol (4 L) and 250 g of charcoal was added. The mixture was heated to reflux for 10 minutes and filtered through a bed of Celite® and the filtrate was concentrated under reduced pressure. The solids were recrystallized twice from acetonitrile (1 L) to yield 580 g (61.8%) of the desired product as an off-white solid.

1. temperaturemaintained the temperature of the reaction mixture below 10° C
2. additionOnce the addition
3. concentrationthe reaction mixture was concentrated under reduced pressure
4. dissolutionThe viscous residue was dissolved in ethyl acetate (4 L)
5. washwashed with water (4 L) and 2M HCl (4 L)
6. customThe organic layer was separated
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. dissolutionThe resulting solid was dissolved in ethanol (4 L)
11. addition250 g of charcoal was added
12. temperatureThe mixture was heated
13. temperatureto reflux for 10 minutes
14. filtrationfiltered through a bed of Celite®
15. concentrationthe filtrate was concentrated under reduced pressure
16. customThe solids were recrystallized twice from acetonitrile (1 L)