Hydrochloric Acid → 2-(4-Difluoromethoxybenzyl)phenol

In a nitrogen stream, an n-butyllithium hexane solution (2.71 M, 3.8 mL) was added dropwise to a solution of 1-benzyloxy-2-bromobenzene (2.5 g, 9.5 mmol) in THF (90 mL) at −78° C. and the mixture solution was stirred at the same temperature for 30 minutes. To this solution, a solution of 4-difluoromethoxybenzaldehyde (1.23 mL, 1.86 mmol) in THF (30 mL) was added dropwise at −78° C. The reaction mixture was stirred at the same temperature for two hours, and then water was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried (anhydrous magnesium sulfate), and then the solvent was distilled under reduced pressure and the obtained residue was treated by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:5)] to obtain a crude product. To a solution of the obtained crude product in methanol (26.8 mL), a 20% palladium hydroxide catalyst (147 mg) was added and furthermore concentrated hydrochloric acid (0.4 mL) was added thereto. The mixture solution was stirred under a hydrogen atmosphere for 24 hours, and then the catalyst was filtered off. The solvent was distilled under reduced pressure and the obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:5)] to obtain the title compound (1.03 g, 42%).

1. stirringThe reaction mixture was stirred at the same temperature for two hours
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with a saturated sodium chloride aqueous solution
4. dry with materialdried (anhydrous magnesium sulfate)
5. distillationthe solvent was distilled under reduced pressure
6. additionthe obtained residue was treated by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:5)]
7. customto obtain a crude product
8. stirringThe mixture solution was stirred under a hydrogen atmosphere for 24 hours
9. filtrationthe catalyst was filtered off
10. distillationThe solvent was distilled under reduced pressure
11. customthe obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:5)]

ORD-Eintrag

ord-1cf4bbf906814d729327ee4d0287d3f7

Quelldatensatz

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08048897B2