Dimethylformamide → Ethyl 2-(4-cyano-3-methoxyphenyl)acetate

Temperatur

80 °C

Ethyl(3-methoxy-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)acetate (16.6 g) was dissolved in anhydrous dimethylformamide (100 mL). Zinc cyanide (3.4 g, 29 mmol) was added, and the solution was purged thoroughly with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (5.6 g, 4.9 mmol) was then added and the reaction mixture was heated to 80° C. for 4 h. After allowing the reaction mixture to cool to ambient temperature and diluting with water (200 mL), ethyl acetate (400 mL) was added and the mixture was filtered to remove any solids. The filtrate was transferred to a separatory funnel, and the layers separated. The aqueous layer was re-extracted with ethyl acetate (2×100 mL). The organic layers were combined and dried over magnesium sulfate. The dry organics were then filtered and evaporated to dryness under reduced pressure and excess dimethylformamide was removed by evaporation in vacuo at 65° C. for 1.5 h to yield crude product. The crude product was purified through silica gel chromatography (ethyl acetate/hexanes, 2:3) to yield ethyl(4-cyano-3-methoxyphenyl)acetate. 1H NMR (500 MHz, DMSO-d6), δ 7.67 (d, J=8.0 Hz, 1H), 7.18 (s, 1H), 7.0 (d, J=8.0 Hz, 1H), 4.10 (q, J=7.1 Hz, 2H), 3.89 (s, 3H), 3.78 (s, 2H), 1.19 (t, J=7.1 Hz, 3H); LC/MS (M+1)+=220.17; tR=1.36 min.

1. customthe solution was purged thoroughly with nitrogen
2. temperatureto cool to ambient temperature
3. additionwas added
4. filtrationthe mixture was filtered
5. customto remove any solids
6. customThe filtrate was transferred to a separatory funnel
7. customthe layers separated
8. extractionThe aqueous layer was re-extracted with ethyl acetate (2×100 mL)
9. dry with materialdried over magnesium sulfate
10. filtrationThe dry organics were then filtered
11. customevaporated to dryness under reduced pressure and excess dimethylformamide
12. customwas removed by evaporation in vacuo at 65° C. for 1.5 h
13. customto yield crude product
14. customThe crude product was purified through silica gel chromatography (ethyl acetate/hexanes, 2:3)

ORD-Eintrag

ord-0d474d2581b14efe9947127835d668e0

Quelldatensatz

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08673920B2