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

Temperatur

80 °C

The crude ethyl(3-methoxy-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)acetate (16.61 g) was subsequently dissolved in anhydrous dimethylformamide (100 mL). Zinc cyanide (3.42 g, 29.1 mmol) was added, and the solution was purged thoroughly with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (5.61 g, 4.85 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. The combined layers were filtered to remove any solids, the filtrate transferred to a separatory funnel, and the layers separated. The aqueous layer was re-extracted with ethyl acetate (2×100 mL), the organic portions 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 the crude title compound (20 g). The crude product was purified through silica gel chromatography (ethyl acetate/hexanes, 2:3) to yield ethyl(4-cyano-3-methoxyphenyl)acetate. 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 combined layers were filtered
5. customto remove any solids
6. customthe filtrate 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 the crude title compound (20 g)
14. customThe crude product was purified through silica gel chromatography (ethyl acetate/hexanes, 2:3)

ORD-Eintrag

ord-64dab7e3d9994977a8c5ee84a1e6e446

Quelldatensatz

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08673920B2