反应详情

To 30 mL of a 1,4-dioxane solution containing 2.4 g of 2-chloro-5-fluoro-3-((methoxymethoxy)methyl)-6-methylpyridine, 2.3 mL of triethylamine, 0.61 mL of formic acid and 0.63 g of tetrakis(triphenylphosphine)palladium(0) were added, and the mixture was stirred for 2 hours with reflux by heating under a nitrogen atmosphere. Thereto was added 30 mL of N,N-dimethylformamide, and the mixture was stirred at 90 to 100° C. for 1 hour. Thereto were added 2.3 mL of triethylamine, 0.61 mL of formic acid and 0.63 g of tetrakis(triphenylphosphine)palladium(0), and the mixture was stirred at 90 to 100° C. for 1 hour. Water and ethyl acetate were added thereto, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, and the resultant solution was washed sequentially with water and an aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by flash silica gel column chromatography [hexane:gradient elution of ethyl acetate=95:5 to 80:20] to obtain 1.8 g of a yellow oily substance, 3-fluoro-5-((methoxymethoxy)methyl)-2-methylpyridine.

1. additionwere added
2. temperaturewith reflux
3. temperatureby heating under a nitrogen atmosphere
4. stirringthe mixture was stirred at 90 to 100° C. for 1 hour
5. stirringthe mixture was stirred at 90 to 100° C. for 1 hour
6. customthe organic layer was separated
7. extractionthe aqueous layer was extracted with ethyl acetate
8. washthe resultant solution was washed sequentially with water
9. dry with materialan aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate
10. customthe solvent was removed under reduced pressure
11. customThe residue thus obtained
12. customwas purified by flash silica gel column chromatography [hexane:gradient elution of ethyl acetate=95:5 to 80:20]