Water → HCID 178517715, compound

As shown in step 3-iii of Scheme 3, 3-(difluoromethoxy)-2-methoxypyridine (270 mg, 1.54 mmol) was dissolved in 5 mL of DCM and BBr3 (540 μL; 1275 mg; 4.10 mmol) in heptane was added. The reaction mixture was stirred for 10 minutes at RT under an atmosphere of nitrogen, brought to reflux, and then stirred an additional 4 hours. The mixture was cooled and water was added to quench the reaction. The pH was adjusted to 7-8 with sodium bicarbonate, the organics partitioned, and the aqueous layer saturated with NaCl and extracted twice more with DCM. The combined organics were dried over Na2SO4, filtered, and the volatiles removed under reduced pressure. The product was purified by silica gel chromatography (DCM to 5% MeOH/DCM gradient) to yield 3-(difluoromethoxy)pyridin-2-ol as a white solid (Compound 1008, 986 mg, 97% yield): ESMS (M+H) 162.

1. temperatureto reflux
2. stirringstirred an additional 4 hours
3. temperatureThe mixture was cooled
4. customto quench
5. customthe reaction
6. extractionthe organics partitioned, and the aqueous layer saturated with NaCl and extracted twice more with DCM
7. dry with materialThe combined organics were dried over Na2SO4
8. filtrationfiltered
9. customthe volatiles removed under reduced pressure
10. customThe product was purified by silica gel chromatography (DCM to 5% MeOH/DCM gradient)

ORD record

ord-87dc2f3a2ca34e65aa1d86eddc9f1506

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08524906B2