3-Pyridinecarboxaldehyde → HCID 22267290, compound

A solution of 3-pyridinecarbaldehyde (2.2 g) in THF (50 ml) was treated dropwise with a solution (50 ml) of Grignard reagent prepared from 1-bromo-4-chloro-2-methoxy-5-methylbenzene (5.0 g) and magnesium (0.8 g) in THF at 0° C., and stirred for 1 hour. The reaction solution was combined with a saturated aqueous solution of ammonium chloride, and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate, and concentrated under reduced pressure. The resultant residue was used in the next step without purification, combined with toluene (150 ml) and manganese dioxide (15 g), and heated under reflux with dehydrating using Deen Stark for 1 hour. After the reaction was completed, the reaction solution was filtered using celite, the filtrate was concentrated under reduced pressure. The resultant residue was combined with methylene chloride (50 ml) and a 1 N solution of BBr3/methylene chloride (60 ml), and stirred at room temperature overnight. After the reaction was completed, water was added, and the solvent was distilled off under reduced pressure. The resultant residue was neutralized with the addition of a saturated aqueous solution of sodium hydrogen carbonate, and then extracted with ethyl acetate. The extract was washed with water, and then dried over magnesium sulfate, and concentrated under reduced pressure. The resultant residue was purified by a silica gel column (eluent: ethyl acetate) to obtain the title compound as an oil (2.4 g).

1. extractionextracted with ethyl acetate
2. washThe extract was washed with water
3. dry with materialdried over magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe resultant residue was used in the next step without purification
6. temperatureheated
7. temperatureunder reflux
8. customfor 1 hour
9. filtrationthe reaction solution was filtered
10. concentrationthe filtrate was concentrated under reduced pressure
11. stirringa 1 N solution of BBr3/methylene chloride (60 ml), and stirred at room temperature overnight
12. additionwater was added
13. distillationthe solvent was distilled off under reduced pressure
14. additionThe resultant residue was neutralized with the addition of a saturated aqueous solution of sodium hydrogen carbonate
15. extractionextracted with ethyl acetate
16. washThe extract was washed with water
17. dry with materialdried over magnesium sulfate
18. concentrationconcentrated under reduced pressure
19. customThe resultant residue was purified by a silica gel column (eluent: ethyl acetate)

ORD record

ord-5165cc1c87e34ca1a75352ec6d0ef0bd

Source dataset

uspto-grants-2005_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06974806B2