Lithium Hydroxide → 5-(3-Hydroxyphenyl)-2-thiophenecarboxamide

Temperatur

0 °C

The mixture of ethyl 5-{3-[(2-oxoethyl)oxy]phenyl}-2-thiophenecarboxylate (1.3 g, 4.48 mmol), 2N aqueous lithium hydroxide solution (5 ml, 10 mmol) and tetrahydrofuran (10 ml) was heated to reflux for 12 h. The reaction mixture was cooled, concentrated in vacuo to remove tetrahydrofuran, acidified to pH1-2 with 2N HCl, and extracted with ethyl acetate three times. The combined extracts were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The solid residue (0.75 g) was dissolved in dry tetrahydrofuran (15 ml) and cooled to 0° C. (Chloromethylene)dimethylammonium chloride (Aldrich, 0.52 g, 4 mmol) was added in one portion. The mixture was stirred at 0° C. for 4 h. The pre-cooled (0° C.) mixture of 28% ammonium hydroxide aqueous solution (2.5 ml) and water (2.5 ml) was added, and the reaction mixture was stirred at the room temperature. Tetrahydrofuran was removed in vacuo and the residue was extracted with ethyl acetate three times. The combined extracts were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (80% ethyl acetate in hexanes) to give the title compound as a brown solid.

1. temperaturewas heated
2. temperatureto reflux for 12 h
3. temperatureThe reaction mixture was cooled
4. concentrationconcentrated in vacuo
5. customto remove tetrahydrofuran
6. extractionextracted with ethyl acetate three times
7. washThe combined extracts were washed with brine
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated in vacuo
10. dissolutionThe solid residue (0.75 g) was dissolved in dry tetrahydrofuran (15 ml)
11. additionwas added in one portion
12. temperatureThe pre-cooled
13. additionwas added
14. stirringthe reaction mixture was stirred at the room temperature
15. customTetrahydrofuran was removed in vacuo
16. extractionthe residue was extracted with ethyl acetate three times
17. washThe combined extracts were washed with brine
18. dry with materialdried over magnesium sulfate
19. concentrationconcentrated in vacuo
20. customThe residue was purified by silica gel column chromatography (80% ethyl acetate in hexanes)

ORD-Eintrag

ord-6f96ae187fc6412192a9d6051bcde140

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08822518B2