2,3-Dimethoxybenzaldehyde → HCID 14986290, compound

Participants

Reaction Steps

To 0.8 g (0.12 g-atoms) of lithium ribbon cut in small pieces in 50 mL of anhydrous ether stirred at room temperature under an argon atmosphere was added 12 g (0.06 mol) of 3-bromo-propan-1-ol 1-ethoxy ethyl ether [P. E. Eaton, G. F. Cooper, R. C. Johnston, and R. H. Mueller, J. Org. Chem. 37, 1947 (1972)]. After about 1 mL was added, the reaction mixture was cooled in an ice-salt bath and the rest of the bromo compound was added dropwise over 35 minutes. Stirring was continued with cooling for 1.5 hours and then 7.5 g (0.045 mol) of 2,3-dimethoxybenzaldehyde in 45 mL of anhydrous ether was added dropwise over 30 minutes. After 1 hour, the cooling bath was removed and stirring was continued at room temperature for 1 hour. The reaction mixture was poured into half-saturated ammonium sulfate solution. The ether layer was separated, dried (Na2SO4) and concentrated to an oil (13.9 g). Ethanol (25 mL), water (25 mL) and 2 mL of concentrated hydrochloric acid were added and the solution was left at room temperature for 35 minutes. Potassium carbonate was added with stirring until the mixture was basic. The ethanol was removed under reduced pressure and the product was extracted with ethyl acetate. The dried extract was concentrated to an oil (12.0 g). This was dissolved in 150 mL of ethanol, 1 g of 10% palladium on carbon was added and the mixture was shaken on a Parr hydrogenator under an initial hydrogen pressure of 55 psi for 5 hours. The reaction mixture was filtered through Celite and the filtrate was concentrated to an oil. Purification by HPLC using 30% ethylacetate-hexane gave 7.45 g (79% yield) of 4-(2,3-dimethoxyphenyl)butan-1-ol.

Provenance & Evidence