3-Hydroxypyridine → HCID 66453928, compound

A suspension of 60% of NaH in oil (2.52 g, 126 mmol) was washed three times with hexanes and the solid was suspended in dry DMF (100 ml). Pyridine-3-ol (10 g, 105 mmol) was slowly added over a period of 5 min and the reaction mixture was stirred at room temperature for about 10 min. The reaction mixture was cooled at 0° C. and 2-bromo-2,2-difluoroacetic acid ethyl ester (21.32 g, 105 mmol) was slowly added. The reaction mixture was heated at 90° C. for 20 h. After cooling the reaction to reach room temperature, ethyl ether was added and the suspension was washed with water and brine. The organic layer was dried over sodium sulfate for 15 min, the solvent was evaporated and the crude was purified by flash chromatography, using 100% methylene chloride to obtain 2,2-difluoro-2-(pyridin-3-yloxy)acetic acid ethyl ester as a brown oil (8 g). 2,2-Difluoro-2-(pyridin-3-yloxy)acetic acid ethyl ester was converted to 2,2-difluoro-2-(pyridin-3-yloxy)acetaldehyde (7 g) by following the procedure described in Example 9, Step 7 above and then converted to the title compound by following Example 1, Steps 8-12 above.

1. washwas washed three times with hexanes
2. temperatureThe reaction mixture was cooled at 0° C.
3. temperatureThe reaction mixture was heated at 90° C. for 20 h
4. temperatureAfter cooling
5. customthe reaction
6. customto reach room temperature
7. washthe suspension was washed with water and brine
8. dry with materialThe organic layer was dried over sodium sulfate for 15 min
9. customthe solvent was evaporated
10. customthe crude was purified by flash chromatography

ORD record

ord-3c41113e001e4283a6b281b126f7043f

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08013186B2