Furfural → 2-(6-Chloro-3-pyridyl)-1-(2-furyl)-1-ethanone

Temperature

-78 °C

To a mixture of 2-furaldehyde (7.9 g, 82.2 mmol) and zinc (II) iodide (110 mg, 0.345 mmol) was dropwise added trimethylsilyl cyanide (11.0 ml, 82.5 mmol) over 10 minutes at 0° C. under an atmosphere of nitrogen gas, followed by stirring as it was. After 30 minutes, the reaction mixture was diluted with tetrahydrofuran (200 ml) and then cooled to −78° C. A 1.0M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (86 ml, 86 mmol) was added dropwise thereto over 1 hour and then a solution of (6-chloro-3-pyridyl)methyl methanesulfonate (18.1 g, 81.7 mmol) in tetrahydrofuran (50 ml) was added dropwise over 1.5 hours thereto, followed by stirring while gradually elevated to room temperature. After 12.5 hours, a 1.0M solution of tetrabutylammonium fluoride in tetrahydrofuran (86 ml, 86 mmol) was added thereto, followed by stirring as it was. After further 30 minutes, the reaction mixture was diluted with a saturated aqueous ammonium chloride solution and ethyl acetate. The resulting organic layer was washed with a saturated aqueous ammonium chloride solution twice, dried over anhydrous sodium sulfate and concentrated. The residue was subjected to silica gel column chromatography (elution solvent; hexane, hexane:ethyl acetate=10:1, 4:1, 3:1, and 2:1) and then suspended in hexane. Subsequently, the resulting precipitates were collected by filtration, to give the title compound (11.9 g, 54%) as a pale brown solid.

1. customover 10 minutes
2. customat 0° C.
3. waitover 1 hour
4. stirringby stirring
5. customwhile gradually elevated to room temperature
6. waitAfter 12.5 hours
7. stirringby stirring as it
8. waitAfter further 30 minutes
9. washThe resulting organic layer was washed with a saturated aqueous ammonium chloride solution twice
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated
12. washThe residue was subjected to silica gel column chromatography (elution solvent; hexane, hexane:ethyl acetate=10:1, 4:1, 3:1, and 2:1)
13. customSubsequently, the resulting precipitates
14. filtrationwere collected by filtration

ORD record

ord-cce8f5a32d82451c912edc119bc641de

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07396836B2