反应详情

A 28% solution of sodium methoxide in methanol (185 mL) was added to 2-fluoro-4-iodo-3,5-dimethylpyridine (97.4 g) in THF (954 mL) at 20° C. The mixture was stirred at 55° C. to 65° C. for two hours. The reaction mixture was cooled and then partitioned by adding MTBE (1 L) and water (1 L). The organic layer was washed with brine. The combined aqueous layers were extracted with MTBE (500 mL×2). The combined organic layers were dried over anhydrous magnesium sulfate. The desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure. n-heptane (50 mL) was added to the residue, and the mixture was stirred at 0° C. for one hour. The precipitated solid was collected by filtration. The solid was washed with cooled n-heptane (10 mL). The title compound (42.6 g) was obtained. The filtrate was concentrated under reduced pressure. n-heptane (5 mL) was added to the residue, and the mixture was stirred at 0° C. for 30 minutes. The precipitated solid was collected by filtration. The solid was washed with cooled n-heptane (2 mL) The title compound (20.2 g) was obtained. The filtrate was concentrated under reduced pressure. n-heptane (5 mL) was added to the residue, and the mixture was stirred at 0° C. for 30 minutes. The precipitated solid was collected by filtration. The solid was washed with cooled n-heptane (2 mL). The title compound (10.7 g) was obtained. The combined title compound (73.5 g) was obtained.

1. temperatureThe reaction mixture was cooled
2. custompartitioned
3. additionby adding MTBE (1 L) and water (1 L)
4. washThe organic layer was washed with brine
5. extractionThe combined aqueous layers were extracted with MTBE (500 mL×2)
6. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
7. customThe desiccant was removed by filtration
8. concentrationthe filtrate was concentrated under reduced pressure
9. additionn-heptane (50 mL) was added to the residue
10. stirringthe mixture was stirred at 0° C. for one hour
11. filtrationThe precipitated solid was collected by filtration
12. washThe solid was washed with cooled n-heptane (10 mL)