反应详情

A mixture of 0.35 g of 5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-oxo-pyridine (step 5 of Example 1), 3 g of phosphorus pentabromide, 0.3 g of potassium bromide and 10 mL of 1,2-dichlorobenzene was held at reflux for 2 hours. The reaction mixture was cooled. An addition 3.7 g of phosphorus pentabromide was added to the reaction mixture and the reaction mixture was held at 90° C. for 8 hours, and at 180°-190° C. for 2 days. The reaction mixture was cooled and stirred with water and methylene chloride. The methylene chloride layer was dried over MgSO4 and filtered through silica gel. The methylene chloride filtrate was concentrated in vacuo and the residue was purified by HPLC (20% ethyl acetate/hexane then 50% ethyl acetate/hexane). The fraction eluted with 50% ethyl acetate/hexane yielded a solid. Recrystallization from methylene chloride/hexane yielded 150 mg of white solid: mp 187.5°-189° C.

1. temperatureat reflux for 2 hours
2. temperatureThe reaction mixture was cooled
3. additionwas added to the reaction mixture
4. waitat 180°-190° C. for 2 days
5. temperatureThe reaction mixture was cooled
6. dry with materialThe methylene chloride layer was dried over MgSO4
7. filtrationfiltered through silica gel
8. concentrationThe methylene chloride filtrate was concentrated in vacuo
9. customthe residue was purified by HPLC (20% ethyl acetate/hexane
10. washThe fraction eluted with 50% ethyl acetate/hexane
11. customyielded a solid
12. customRecrystallization from methylene chloride/hexane