Water → 5-Methoxy-2-methylpyridine

6-methylpyridin-3-ol (50.0 g, 0.458 mol) was added to a suspension of powdered KOH (103 g, 1.83 mol) in dimethylsulfoxide (750 mL) and the mixture was left to stir at room temperature under nitrogen for 1.5 hours. Methyl iodide (30 mL, 68.3 g, 0.481 mol) was then added dropwise over 1 hour to the dark brown mixture (exothermic). After stirring at room temperature for 1.5 hours water (1.0 L) was added and the mixture was extracted with ethyl acetate (2×300 mL). The combined organic extracts were washed with brine, dried (MgSO4) and evaporated at 40° C. on a rotary evaporator. The residue was purified by column chromatography (silica), eluting with pentane, increasing polarity to ethyl acetate, to give the volatile product as a ˜1:1 mixture with ethyl acetate (40 g, ˜23.3 g product, 41%). 1H NMR (CDCl3, 400 MHz) δ 2.45 (3H, s), 3.79 (3H, s), 7.02 (1H, d), 7.08 (1H, dd), 8.16 (1H, d).

1. waitthe mixture was left
2. additionwas added
3. extractionthe mixture was extracted with ethyl acetate (2×300 mL)
4. washThe combined organic extracts were washed with brine
5. dry with materialdried (MgSO4)
6. customevaporated at 40° C. on a rotary evaporator
7. customThe residue was purified by column chromatography (silica)
8. washeluting with pentane
9. temperatureincreasing polarity to ethyl acetate
10. customto give the volatile product as a ˜1:1 mixture with ethyl acetate (40 g, ˜23.3 g product, 41%)

ORD record

ord-03352f9714d24273a6dabd1c0b87f4ae

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08138188B2