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

The preparation was conducted according to the description in the document (J. Med. Chem., (1994), 37, 3977-3985). Sodium hydride (3.36 g, 55%, 77.0 mmol) was added to a DMF (100 mL) solution of 2,2-difluoroethanol (5.75 g, 70.0 mmol) under ice-cooling over 5 minutes under a nitrogen gas flow. The resulting mixture was stirred at the same temperature for 10 minutes, and then to the reaction solution was dropwise added a DMF (40 mL) solution of 4-fluorobenzaldehyde (9.56 g, 77.0 mmol) over 5 minutes. The mixture was stirred at room temperature for 4 hours, and the reaction solution was poured into ice water (500 mL). The resulting mixture was extracted with ether:n-hexane (300 mL, 1:1, V/V) three times. The extracted organic layer was washed with water (300 mL) three times and with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to give a crude product. A solution mixture of ether:n-hexane (20 mL, 1:10, V/V) was added to this crude product, and the supernatant was removed. This procedure was repeated four times in total to wash the crystalline product to give 10.1 g of the title compound (colorless crystal, yield: 77%).

1. temperaturecooling over 5 minutes under a nitrogen gas flow
2. stirringThe mixture was stirred at room temperature for 4 hours
3. extractionThe resulting mixture was extracted with ether
4. washThe extracted organic layer was washed with water (300 mL) three times and with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customThe solvent was evaporated
7. customto give a crude product
8. customthe supernatant was removed
9. washto wash the crystalline product

ORD-Eintrag

ord-822b819a9f8148b2b8f959fbb210fd99

Quelldatensatz

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08344029B2