Hydrochloric Acid → 2-Ethyl-3-methoxybenzaldehyde

Temperatur

-15 °C

To a solution of 2,2,6,6-tetramethylpiperidine (4.67 g, 33 mmol) in 75 ml THF at −15° C. was added n-butyllithium (12.6 ml, 32 mmol, 2.5 in hexanes) drop-wise maintaining the internal temperature below −10° C. After 15 min a solution of cyclohexyl-(3-methoxy-benzylidene)-amine (3.259 g, 15.0 mmol) in 5.0 ml THF was added and the solution was allowed to stir at −15° C. After 1 h the solution was cooled to −78° C. Iodoethane (11.9 ml, 150 mmol) was added in one portion and the solution was allowed to warm to rt over 45 min, poured into 10% NH4Cl, and extracted with Et2O. The combined organics were washed with H2O, washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give a crude imine as an oil. The oil was taken up in 90 ml of THF and HCl (22 ml, 89 mmol, 4.0 M) and warmed to reflux. After 2 the solution was cooled. H2O was added and the mixture was extracted with ethyl acetate. The combined organics were washed with H2O, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give a crude oil. Purification via flash chromatography (98:2 hexane/ethyl acetate) gave 2-ethyl-3-methoxy benzaldehyde (1.543 g, 63%, 2 steps) as a clear oil.

1. temperaturedrop-wise maintaining the internal temperature below −10° C
2. temperatureAfter 1 h the solution was cooled to −78° C
3. temperatureto warm to rt over 45 min
4. extractionextracted with Et2O
5. washThe combined organics were washed with H2O
6. washwashed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto give a crude imine as an oil
11. temperatureAfter 2 the solution was cooled
12. extractionthe mixture was extracted with ethyl acetate
13. washThe combined organics were washed with H2O
14. washwashed with brine
15. dry with materialdried over Na2SO4
16. filtrationfiltered
17. concentrationconcentrated in vacuo
18. customto give a crude oil
19. customPurification via flash chromatography (98:2 hexane/ethyl acetate)

ORD-Eintrag

ord-ba49046829ca48738843f8ff099ce829

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08524725B2