Benzyl Chloride → 2-(Benzyloxy)-3-methoxybenzaldehyde

A 60% dispersion of sodium hydride in mineral oil (5.26 g, 140 mmol) was washed with hexane and the hexane was removed. To the washed sodium hydride was added 75 mL of anhydrous DMF. The resultant slurry was well stirred and 21.38 g (140 mmol) of 2-hydroxy-3-methoxy benzaldehyde (commercially available from Aldrich Chemical Company) was added dropwise, over a period of 45 minutes. The mixture was stirred at 50° C. for 1 h and then 16.2 mL (140 mmol) of benzyl chloride was added in one portion. The reaction mixture was stirred at 50° C. for 3 days and then allowed to slowly (overnight) cool to ambient temperature and the reaction was quenched with 60 mL of 10% aqueous hydrochloric acid solution. The mixture was extracted with 3×250 mL of ethyl acetate and the combined ethyl acetate extracts were washed with 250 mL of aqueous sodium bicarbonate solution, water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel eluted with ethyl acetate:hexane (1:9 v/v) to give 26.39 g (77.5%) of the title compound.

1. customthe hexane was removed
2. additionTo the washed sodium hydride was added 75 mL of anhydrous DMF
3. stirringThe mixture was stirred at 50° C. for 1 h
4. stirringThe reaction mixture was stirred at 50° C. for 3 days
5. customallowed to slowly (overnight)
6. customthe reaction was quenched with 60 mL of 10% aqueous hydrochloric acid solution
7. extractionThe mixture was extracted with 3×250 mL of ethyl acetate
8. washthe combined ethyl acetate extracts were washed with 250 mL of aqueous sodium bicarbonate solution, water and brine
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by chromatography on silica gel
13. washeluted with ethyl acetate:hexane (1:9 v/v)

ORD record

ord-196799f8ad5148f2a1f4a849d2afc7ce

Source dataset

uspto-grants-1991_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04994486