反应详情

温度

142.5 °C

Neat POCl3 (400 mL) was added to 8-methoxyquinazolin-2-ol (5.0 g, 28.4 mmole) with stirring and cooling over an ice bath under argon. After ca. 1 minute, the reaction was removed from the ice bath and stirred at RT for ca. 20 minutes until a fine yellow suspension was formed. The reaction, fitted with a reflux condenser, was heated in an oil bath at 140-145° C. After about 1 hour, the reaction turned clear and colorless. LCMS showed that the reaction was complete. The POCl3 was evaporated under reduced pressure, and dried in vacuo. After 12 hours, the residue was partitioned between EtOAc (300 mL) and sat. NaHCO3 (200 mL). The mixture was stirred cautiously watching gas evolution until the pH reached ˜8. The layers were separated and the organic layer was washed with NaHCO3 (2×100 mL), water with 5% brine (2×100 mL), brine (100 mL), dried (Na2SO4), filtered and evaporated to a yellow solid. The crude product was purified by flash chromatography eluting with 50% EtOAc/Hexane and finishing with 100% EtOAc to produce a white solid after evaporating the correct fractions. The pure 2-chloro-8-methoxyquinazoline was isolated in 89% yield (4.9 g, 25.3 mmole).

1. temperaturecooling over an ice bath under argon
2. customthe reaction was removed from the ice bath
3. stirringstirred at RT for ca. 20 minutes until a fine yellow suspension
4. customwas formed
5. customThe reaction
6. customfitted with a reflux condenser
7. waitAfter about 1 hour
8. customThe POCl3 was evaporated under reduced pressure
9. customdried in vacuo
10. waitAfter 12 hours
11. customthe residue was partitioned between EtOAc (300 mL) and sat. NaHCO3 (200 mL)
12. stirringThe mixture was stirred cautiously
13. customThe layers were separated
14. washthe organic layer was washed with NaHCO3 (2×100 mL), water with 5% brine (2×100 mL), brine (100 mL)
15. dry with materialdried (Na2SO4)
16. filtrationfiltered
17. customevaporated to a yellow solid
18. customThe crude product was purified by flash chromatography
19. washeluting with 50% EtOAc/Hexane
20. customto produce a white solid
21. customafter evaporating the correct fractions