Hexamethylenetetramine → 3,5-Difluoro-4-hydroxybenzaldehyde

A solution of 2,6-difluorophenol (25 g, 192 mmol), hexamethylenetetramine (26 g, 192 mmol) and trifluoroacetic acid (190 mmol) was refluxed overnight. The reaction was cooled and diluted with water (200 mL) and extracted with dichloromethane (3×100 mL). The organic layer was washed with 10% aqueous potassium carbonate (2×100 mL). The aqueous layer was acidified with concentrated hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to yield 3,5-difluoro-4-hydroxybenzaldehyde as a white solid. Upon sitting the desired product began to precipitate from the original aqueous layer that was extracted with dichloromethane. The layer was filtered to provide the product (6) as long white crystals.

1. temperatureThe reaction was cooled
2. extractionextracted with dichloromethane (3×100 mL)
3. washThe organic layer was washed with 10% aqueous potassium carbonate (2×100 mL)
4. extractionextracted with ethyl acetate
5. dry with materialThe organic layer was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-b4274c3f135d4fa1bb09f786631053b7

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598374B2