3-Pyridinecarboxaldehyde → 4-Chloromethyl-5-methyl-2-(pyridin-3-yl)oxazole

A mixture of pyridine-3-carbaldehyde (26.26 g), 2,3-butanedione-2-oxime (24.77 g) and 4N hydrogenchloride-ethyl acetate solution (300 mL) was stirred at room temperature for 3 days. The reaction mixture was concentrated, and the obtained crystals were washed with diethyl ether. To the crystals was added tetrahydrofuran (250 mL), and a solution of thionyl chloride (43.78 g) in tetrahydrofuran (50 mL) was further added. The mixture was heated under reflux for 3 hrs. The reaction mixture was concentrated and ethyl acetate was added to the residue. The ethyl acetate layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give 3-(4-chloromethyl-5-methyl-1,3-oxazol-2-yl)pyridine as colorless crystals (9.48 g, 19%) from a fraction eluted with ethyl acetate-hexane (1:1, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 87-88° C.

1. concentrationThe reaction mixture was concentrated
2. washthe obtained crystals were washed with diethyl ether
3. additionTo the crystals was added tetrahydrofuran (250 mL)
4. additiona solution of thionyl chloride (43.78 g) in tetrahydrofuran (50 mL) was further added
5. temperatureThe mixture was heated
6. temperatureunder reflux for 3 hrs
7. concentrationThe reaction mixture was concentrated
8. additionethyl acetate was added to the residue
9. washThe ethyl acetate layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine
10. dry with materialdried over anhydrous magnesium sulfate
11. concentrationconcentrated

ORD record

ord-ac74abb67bab47d5b937339c6d549acb

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07368578B2