反应详情

温度

50 °C

To 2,2,2-trifluoro-1-(3′-fluorobiphenyl-4-yl)ethanol (1.4 g, 5.18 mmol) in THF (50 mls) at 0° C. was added NaH (60% in mineral oil, 0.31 g, 7.77 mmol). The ice bath was removed and the mixture was stirred for 30 minutes. 2-Amino-4,6-dichloropyrimidine (1.0 g, 6.22 mmol) in THF (25 mls) was added at once. The mixture was heated to 50° C. for 5 hours. The reaction was complete by LCMS (Sunfire, TFA). The mixture was cooled, quenched with brine, and extracted 3 times with CH2Cl2. The organics were combined, washed with brine, dried over MgSO4, and concentrated. Chromatography (SiO2, CH2Cl2) afforded 1.48 g of 4-chloro-6-(2,2,2-trifluoro-1-(3′-fluorobiphenyl-4-yl)ethoxy)pyrimidin-2-amine. Yield 73%.

1. customThe ice bath was removed
2. temperatureThe mixture was cooled
3. customquenched with brine
4. extractionextracted 3 times with CH2Cl2
5. washwashed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated