Pyridine → 3-Hydroxy-4-iodobenzonitrile

22.3 g (89.7 mmol) of 3-hydroxy-4-iodobenzoic acid was dissolved in 300 ml of tetrahydrofuran. 19.7 ml (206 mmol) of ethyl chloroformate and 28.7 ml (206 mmol) of triethylamine was added to the solution at 0° C. After stirring for 15 minutes, the obtained triethylamine hydrochloride was taken by the filtration. The filtrate was added to 300 ml of tetrahydrofuran solution, in which ammonia had been bubbled, at 0° C. After stirring at room temperature for 18 hours, the solvent was evaporated under reduced pressure. The residue was dissolved in 450 ml of dioxane. 17.4 ml (117 mmol) of Trifluoromethanesulfonic anhydride and 21.8 ml (269 mmol) of pyridine were added to the solution at 0° C. After stirring at room temperature for 18 hours, the solvent was evaporated under reduced pressure. The residue was treated with chloroform as the extractant by an ordinary method to obtain an oily residue. This residue was dissolved in 180 ml of tetrahydrofuran/methanol (1:1). 90 ml (90.0 mmol) of 1 N aqueous sodium hydroxide solution was added to the solution at room temperature. After stirring under these conditions for 4 hours, the solvent was evaporated under reduced pressure, and the residue was washed with dichloromethane. The residue was acidified with 1 N aqueous hydrogen chloride solution, and treated with ethyl acetate as the extractant by an ordinary method to obtain the crude product, which was purified by the silica gel column chromatography to obtain the title compound.

1. filtrationthe obtained triethylamine hydrochloride was taken by the filtration
2. additionThe filtrate was added to 300 ml of tetrahydrofuran solution, in which ammonia
3. customhad been bubbled, at 0° C
4. stirringAfter stirring at room temperature for 18 hours
5. customthe solvent was evaporated under reduced pressure
6. dissolutionThe residue was dissolved in 450 ml of dioxane
7. stirringAfter stirring at room temperature for 18 hours
8. customthe solvent was evaporated under reduced pressure
9. additionThe residue was treated with chloroform as the extractant by an ordinary method
10. customto obtain an oily residue
11. stirringAfter stirring under these conditions for 4 hours
12. customthe solvent was evaporated under reduced pressure
13. washthe residue was washed with dichloromethane
14. additiontreated with ethyl acetate as the extractant by an ordinary method
15. customto obtain the crude product, which
16. customwas purified by the silica gel column chromatography

ORD record

ord-f9f8099343584219bb603ad92d09f7d4

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07396844B1