Tetrahydrofuran → Ethyl 3-(4-Hydroxy-3,5-Dimethoxyphenyl)Acrylate

To a stirred solution of triethyl phosphonoacetate (0.60 mL, 3.02 mmol) in THF (5 mL) was added portion-wise NaH (60% dispersion in mineral oil, 360 mg, 9.00 mmol) over 2-3 mins. After effervescence had ceased, 4-hydroxy-3,5-dimethoxybenzaldehyde (547 mg, 3.00 mmol) was added portion-wise, washing in with THF (3 mL). More THF (2×2 mL) was added to the thick slurry and the resulting mixture was then heated to reflux for 21 hours. The mixture was then allowed to cool slowly to ambient temperature and the reaction quenched by the careful addition of saturated aqueous NH4Cl (20 mL). The organic solvent was then removed under vacuum and the resulting aqueous mixture was then extracted with DCM (10 mL, 5 mL and then 2 mL) using hydrophobic frits. The filtrate was then treated with Polymer Supported-TsNHNH2 resin (loading 3.22 mmol/g, 1.62 g, 5.23 mmol (3 eq wrt unreacted aldehyde)) and the mixture stirred for 16 hours to remove any unreacted aldehyde. The resin was then removed by filtration washing with DCM (5 mL, 10 mL and then 5 mL) and the filtrate reduced under vacuum to give the title compound (221 mg).

1. washwashing in with THF (3 mL)
2. additionMore THF (2×2 mL) was added to the thick slurry
3. temperaturethe resulting mixture was then heated
4. temperatureto reflux for 21 hours
5. customthe reaction quenched by the careful addition of saturated aqueous NH4Cl (20 mL)
6. customThe organic solvent was then removed under vacuum
7. extractionthe resulting aqueous mixture was then extracted with DCM (10 mL, 5 mL
8. customto remove any unreacted aldehyde
9. customThe resin was then removed by filtration
10. washwashing with DCM (5 mL, 10 mL

ORD-Eintrag

ord-98ffb6f561f64b1982844057862db2a3

Quelldatensatz

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07338960B2