2,4-Dihydroxybenzaldehyde → 4-(4-Chloro-benzyloxy)-2-hydroxybenzaldehyde

Temperature

90 °C

A mixture of 2,4-dihydroxybenzaldehyde (6.62 g, 48 mmol, Fluka), potassium fluoride (5.57 g, 96 mmol, Aldrich) and 4-chlorobenzyl chloride (13.50 g, 84 mmol, Aldrich) in acetonitrile (50 mL) was heated at 90° C. for 24 hours. After cooling, the mixture was partitioned between ether (2×100 mL) and water (2×100 mL). Organic layers were washed with brine (100 mL), combined, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (Biotage 75S, hexanes, then hexanes-dichloromethane 1:1 as solvent) to give partial separation. Pure fractions of product were combined and concentrated and the residue crystallized from hexanes with traces of dichloromethane to give 4-(4-chloro-benzyloxy)-2-hydroxy-benzaldehyde as white crystals. (Yield 4.74 g). Mother liquor and impure fractions were combined and further purified by flash chromatography (Biotage 40L, same solvent as before) and pure fractions were combined and concentrated. The residue was re-crystallized to give second crop of 4-(4-chloro-benzyloxy)-2-hydroxy-benzaldehyde. (Yield 3.03 g).

1. temperatureAfter cooling
2. customthe mixture was partitioned between ether (2×100 mL) and water (2×100 mL)
3. washOrganic layers were washed with brine (100 mL)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by flash chromatography (Biotage 75S, hexanes
8. customhexanes-dichloromethane 1:1 as solvent) to give partial
9. customseparation
10. concentrationconcentrated
11. customthe residue crystallized from hexanes with traces of dichloromethane

ORD record

ord-53198408ebea4c9f907dae617b068106

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968554B2