2,3-Dimethoxybenzaldehyde → HCID 14986290, compound

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.

1. additionAfter about 1 mL was added
2. temperaturethe reaction mixture was cooled in an ice-salt bath
3. temperaturewith cooling for 1.5 hours
4. customthe cooling bath was removed
5. stirringstirring
6. waitwas continued at room temperature for 1 hour
7. additionThe reaction mixture was poured into half-saturated ammonium sulfate solution
8. customThe ether layer was separated
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated to an oil (13.9 g)
11. additionEthanol (25 mL), water (25 mL) and 2 mL of concentrated hydrochloric acid were added
12. waitthe solution was left at room temperature for 35 minutes
13. additionPotassium carbonate was added
14. stirringwith stirring until the mixture
15. customThe ethanol was removed under reduced pressure
16. extractionthe product was extracted with ethyl acetate
17. extractionThe dried extract
18. concentrationwas concentrated to an oil (12.0 g)
19. dissolutionThis was dissolved in 150 mL of ethanol
20. addition1 g of 10% palladium on carbon was added
21. stirringthe mixture was shaken on a Parr hydrogenator under an initial hydrogen pressure of 55 psi for 5 hours
22. filtrationThe reaction mixture was filtered through Celite
23. concentrationthe filtrate was concentrated to an oil
24. customPurification by HPLC

ORD record

ord-c0938b948c0e4b42abf62797cbfeec03

Source dataset

uspto-grants-1991_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05025036