Diisobutylaluminumhydride → (4-Chloro-3-ethoxyphenyl)methanol

Participants

Reaction Conditions

Reaction Steps

The title compound was prepared from commercially available 4-chloro-3-hydroxy-benzoic acid as follows: 4-chloro-3-hydroxy-benzoic acid (3.0 g, 17 mmol) was dissolved in DMF (15 ml) and K2CO3 (4.7 g, 34.0 mmol) and EtI (6.0 g, 38 mmol) were added and the reaction stirred for 6 h. The reaction was then diluted with water and extracted with EtOAc. The organic extracts were dried (Na2SO4) and concentrated to afford 3.6 g (91% yield) of 4-chloro-3-ethoxy-benzoic acid ethyl ester. The crude ester was then dissolved in THF (20 mL) and cooled to −78° C. under Ar. Di-isobutylaluminium hydride (95 mL, 1M in THF, 95 mmol) was then slowly added (15 min), the cooling bath removed on completion of addition and the reaction allowed to reach 0° C. (1 h). The reaction was then cooled to −78° C., the excess hydride was quenched by cautious addition of 1N HCl. The mixture was brought to room temperature, the organic separated and the aqueous extracted with EtOAc. The combined organic were dried (Na2SO4) and concentrated to afford 2.9 g (100% yield) of 4-chloro-3-ethoxy-benzyl alcohol. 2.94 g (16 mmol) of the crude alcohol was dissolved in DCM (15 mL) and MnO2 (5.5 g, 63 mmol) was added. The reaction was stirred for 16 h, after which time the reaction was filtered through Hyflo and concentrated. The residue was purified by flash column chromatography (EtOAc:Heptane 1:4) to yield 1.5 g (52% yield) of the title aldehyde.

Provenance & Evidence