Methanol → 2-Methyl-5-phenoxypyridine

To a solution of 6-methylpyridin-3-ol (25.2 g, 231 mmol) in N,N-dimethylformamide (100 ml) was added potassium tert-butoxide (25.9 g, 231 mmol), and the mixture was stirred at room temperature for 1 hr. The reaction solution was evaporated under reduced pressure and diluted with N,N-dimethylformamide (100 ml). A copper powder (3.7 g, 58 mmol) and bromobenzene (36.3 g, 231 mmol) were added, and the mixture was stirred at 120° C. overnight. Methanol was added to the reaction solution and insoluble material was filtered off using celite. The filtrate was diluted with water (500 ml) and the mixture was extracted with ethyl acetate (500 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give the objective substance (31 g, 72%).

1. customThe reaction solution was evaporated under reduced pressure
2. additiondiluted with N,N-dimethylformamide (100 ml)
3. stirringthe mixture was stirred at 120° C. overnight
4. filtrationwas filtered off
5. additionThe filtrate was diluted with water (500 ml)
6. extractionthe mixture was extracted with ethyl acetate (500 ml×2)
7. washThe extract was washed successively with water and saturated brine
8. dry with materialdried (anhydrous magnesium sulfate)
9. customevaporated under reduced pressure
10. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)
11. customto give the objective substance (31 g, 72%)

ORD record

ord-830997d5bae4401a860bf652c9124cef

Source dataset

uspto-grants-2006_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06982348B2