تفاعل #40990

معادلة التفاعل

5-bromo-2,4-bis(methyloxy)pyrimidine

2-fluoropyridine-3-boronic acid

boronic acid

potassium carbonate

→

title compound

المردود 93.1%

5-(2-fluoro-3-pyridinyl)-2,4-bis(methyloxy)pyrimidine

المردود 93.1%

المذيبات

AcOEt

water

1,4-Dioxane

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwas added
2. 2
   أخرىThe mixture was degassed with Argon
3. 3
   درجة الحرارةThen the mixture was cooled down
4. 4
   workup.ADDITIONwere added
5. 5
   درجة الحرارةthe mixture heated at 100° C. for two 2 h
6. 6
   درجة الحرارةThe reaction mixture was cooled down to room temperature
7. 7
   استخلاصThe aqueous layer was back extracted with AcOEt
8. 8
   تجفيفThe combined organics were dried over Na2SO4
9. 9
   أخرىevaporated to dryness
10. 10
    أخرىThe crude material was purified by SiO2 flash chromatography
11. 11
    غسيلeluting with Cy/EA 8/2

الإجراء التجريبي

To a mixture of 5-bromo-2,4-bis(methyloxy)pyrimidine (Prep86, 3 g, 13.70 mmol), 2-fluoropyridine-3-boronic acid (1.930 g, 13.70 mmol) and Pd(PPh3)4 (0.791 g, 0.685 mmol), dry 1,4-Dioxane (45 ml) was added followed by potassium carbonate 1M solution (27.4 ml, 27.4 mmol). The mixture was degassed with Argon and then heated at 100° C. for 1 h (internal T˜90° C.). Then the mixture was cooled down to ambient, further 1 eq of boronic acid (1.930 g, 13.70 mmol) followed by 5 mol % of PdTetrakis (0.791 g, 0.685 mmol) were added and the mixture heated at 100° C. for two 2 h. The reaction mixture was cooled down to room temperature, taken up with water and AcOEt. The aqueous layer was back extracted with AcOEt. The combined organics were dried over Na2SO4 and evaporated to dryness. The crude material was purified by SiO2 flash chromatography eluting with Cy/EA 8/2 to get the title compound as white solid (3 g).

المصدر