反应详情

温度

50 °C

7b (120 g, 0.271 mol), 1d (128.34 g, 0.407 mol) and K2CO3 (93.64 g, 0.407 mol) were charged to the reaction vessel under an inert atmosphere and suspended in DMF. The resulting slurry was warmed to 50° C. and stirred for 17 hours. The reaction was incomplete so additional 1d (50 g, 0.158 mol) and DMF (300 mL) were added. The reaction was complete after 32 hours and the mixture was cooled to RT. i-PrOAc (1 L) and water (1 L) were added and stirred for 30 minutes. The layers were separated and MeSO3H (52.8 mL, 0.813 mol) was added slowly to the organic layer controlling the exotherm (24.4° C. to 41.0° C.). The mixture warmed to 60° C. and was stirred for 3 hours. The mixture was cooled to RT and was added slowly to a mixture of K2CO3 (186.99 g, 1.35 mol) in water (975 mL). After stirring for 15 minutes, the organic layer was separated and extracted with a H3PO4 solution (94 g of 85% H3PO4 in 975 mL water). The aqueous layer was slowly added to K2CO3 (186.99 g, 1.35 mol) in water (975 mL), followed by i-PrOAc (1100 mL). The mixture was stirred for 10 minutes and the layers separated. The i-PrOAc layer was dried (NaSO4) and concentrated to give 3-((R)-2-amino-2-phenyl-ethyl)-5-(2-chloro-3-methoxy-phenyl)-1-(2-fluoro-6-methyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione 7c as a foaming solid (145.5 g, 0.25 mol, 95% crude yield, uncorrected for purity).

1. additionwere added
2. waitThe reaction was complete after 32 hours
3. temperaturethe mixture was cooled to RT
4. stirringstirred for 30 minutes
5. customThe layers were separated
6. customthe exotherm (24.4° C. to 41.0° C.)
7. temperatureThe mixture warmed to 60° C.
8. stirringwas stirred for 3 hours
9. temperatureThe mixture was cooled to RT
10. stirringAfter stirring for 15 minutes
11. customthe organic layer was separated
12. extractionextracted with a H3PO4 solution (94 g of 85% H3PO4 in 975 mL water)
13. stirringThe mixture was stirred for 10 minutes
14. customthe layers separated
15. dry with materialThe i-PrOAc layer was dried (NaSO4)
16. concentrationconcentrated