3,4-Dihydroxybenzaldehyde → 4-(Difluoromethoxy)-3-hydroxybenzaldehyde

Temperature

120 °C

Commercially available 3,4-dihydroxybenzaldehyde (5 g, 36.2 mmol) and commercially available sodium chlorodifluoroacetate (5.57 g, 36.5 mmol) were dissolved in N,N-dimethylformamide (45 mL) and water (905 μL), and then sodium hydroxide (1.48 g, 37.0 mmol) was added at room temperature, and the mixture was heated and stirred at 120° C. for 2 hours. The solvent was evaporated under vacuum, the residue was cooled to 0° C., and 5 M hydrochloric acid and diethyl ether were added for partition. The organic layer was washed with water and a saturated saline solution, and then the solvent was evaporated. The residue was dissolved in dichloromethane and the resultant was purified with silica gel column chromatography (n-heptane:ethyl acetate 9:1-7:3), and then the target fraction was concentrated under vacuum to obtain the title compound (2.66 g, 39%).

1. temperaturethe mixture was heated
2. customThe solvent was evaporated under vacuum
3. temperaturethe residue was cooled to 0° C.
4. addition5 M hydrochloric acid and diethyl ether were added
5. customfor partition
6. washThe organic layer was washed with water
7. customa saturated saline solution, and then the solvent was evaporated
8. dissolutionThe residue was dissolved in dichloromethane
9. customthe resultant was purified with silica gel column chromatography (n-heptane:ethyl acetate 9:1-7:3)
10. concentrationthe target fraction was concentrated under vacuum

ORD record

ord-2e99acfe22304685b8b2b542d037d906

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933099B2