2,3,5-Trimethylpyridine → 3,5-Dimethylpyridine-2-carbaldehyde

Temperature

0 °C

In dichloromethane (15.0 ml), 2,3,5-trimethyl-pyridine (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (1.29 g) was dissolved. After having been cooled to 0° C., the reaction solution was added with m-chloroperbenzoic acid (2.53 g), followed by stirring at room temperature for 1.5 hours. The reaction solution was added with a 1 mol/l sodium hydroxide aqueous solution and then subjected to extraction with chloroform. Subsequently, the organic layer was washed with a saturated saline solution and dried with anhydrous sodium sulfate. The drying agent was filtrated out and the solvent was then distilled off, followed by dissolving the resultant residue in dichloromethane (25.0 ml). The reaction solution was added with trifluoroacetic anhydride (2.8 ml) and the whole was refluxed under heating for 3.5 hours. After the reaction solution was cooled to room temperature, the solvent was distilled off. The resultant residue was dissolved in methanol (60.0 ml). After having been cooled to 0° C., the reaction solution was added with a 12.5% sodium methoxide/methanol solution to adjust the solution to pH 10, and the whole was stirred at room temperature for 16.5 hours. After the solvent was distilled off, the residue was added with distilled water and subjected to extraction with chloroform. The organic layer was washed with a saturated saline solution and dried with anhydrous sodium sulfate. The drying agent was filtrated out and the solvent was then distilled off, followed by dissolving the residue in chloroform (30.0 ml). The reaction solution was added with manganese dioxide (chemically processed product) (6.10 g) and then stirred at room temperature for 18 hours. The reaction solution was filtrated through Celite. The solvent in the filtrate was distilled off and the resultant residue was then purified through silica gel column chromatography (chloroform/ethyl acetate), thereby obtaining the subject compound (1.14 g) as a yellow oily substance.

1. extractionsubjected to extraction with chloroform
2. washSubsequently, the organic layer was washed with a saturated saline solution
3. dry with materialdried with anhydrous sodium sulfate
4. filtrationThe drying agent was filtrated out
5. distillationthe solvent was then distilled off
6. dissolutionby dissolving the resultant residue in dichloromethane (25.0 ml)
7. additionThe reaction solution was added with trifluoroacetic anhydride (2.8 ml)
8. temperaturethe whole was refluxed
9. temperatureunder heating for 3.5 hours
10. temperatureAfter the reaction solution was cooled to room temperature
11. distillationthe solvent was distilled off
12. dissolutionThe resultant residue was dissolved in methanol (60.0 ml)
13. temperatureAfter having been cooled to 0° C.
14. additionthe reaction solution was added with a 12.5% sodium methoxide/methanol solution
15. stirringthe whole was stirred at room temperature for 16.5 hours
16. distillationAfter the solvent was distilled off
17. additionthe residue was added with distilled water
18. extractionsubjected to extraction with chloroform
19. washThe organic layer was washed with a saturated saline solution
20. dry with materialdried with anhydrous sodium sulfate
21. filtrationThe drying agent was filtrated out
22. distillationthe solvent was then distilled off
23. dissolutionby dissolving the residue in chloroform (30.0 ml)
24. additionThe reaction solution was added with manganese dioxide (chemically processed product) (6.10 g)
25. stirringstirred at room temperature for 18 hours
26. filtrationThe reaction solution was filtrated through Celite
27. distillationThe solvent in the filtrate was distilled off
28. customthe resultant residue was then purified through silica gel column chromatography (chloroform/ethyl acetate)

ORD record

ord-27da2ae8f9d64847ab7d7ebe92910d65

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07932281B2