Dimethylformamide → 4-(2,2-Difluoroethoxy)benzaldehyde

With reference to the document (J. Med. Chem., (1994), 37, 3977-3985), sodium hydride (3.36 g, 55%, 77.1 mmol) was added to a solution of DMF (100 mL) containing 2,2-difluoroethanol (5.75 g, 70.1 mmol) over 5 minutes under nitrogen gas flow under ice-cooling. The mixture was stirred at the same temperature for 10 minutes, and then a solution of DMF (40 mL) containing 4-fluorobenzaldehyde (9.56 g, 77.0 mmol) was added dropwise thereto over 5 minutes. The mixture was stirred at room temperature for 4 hours and was then poured into ice water (500 mL). The resulting mixture was extracted with ether:hexane (300 mL, 1:1, v/v) three times. The extracted organic layer was washed with water (300 mL) three times and then with saturated brine, and was dried over anhydrous magnesium sulfate. Then, the solvent was evaporated to give a crude product. An ether/hexane mixture solution (20 mL, 1:10, v/v) was added to the crude product, and the supernatant fluid was removed. This procedure was repeated four times in total to wash the crystals to give 10.1 g of the title compound (colorless crystalline solid, yield: 77%).

1. temperaturecooling
2. additionwas added dropwise
3. waitover 5 minutes
4. stirringThe mixture was stirred at room temperature for 4 hours
5. extractionThe resulting mixture was extracted with ether
6. washThe extracted organic layer was washed with water (300 mL) three times
7. dry with materialwith saturated brine, and was dried over anhydrous magnesium sulfate
8. customThen, the solvent was evaporated
9. customto give a crude product
10. customthe supernatant fluid was removed
11. washto wash the crystals

ORD record

ord-6565893fa1c44260b82e8d96ec94e24a

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08497397B2