反应详情

温度

0 °C

To a solution of 7-hydroxy-hept-2-enoic acid ethyl ester (99.9 g, 0.58 mol) in tetrahydrofuran prepared in the previous step, cooled with ice-water bath, was added sodium hydride (4.80 g, 0.12 mol, 60%) in two portions. The mixture was stirred at 0° C. for 2 h and then at room temperature for 2 h. The mixture was neutralized with a 1 M aqueous hydrochloric acid solution (pH ˜5.0-6.0). Water (1 L) was then added and the mixture was extracted with ethyl acetate (3×1 L). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was treated with hexanes/ethyl acetate (3×800 mL, hexanes/ethyl acetate=10/1, v/v). The mixture was filtered and dried over anhydrous sodium sulfate. The filtrate was concentrated and the crude product was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 10% ethyl acetate/hexanes) to afford (tetrahydro-pyran-2-yl)-acetic acid ethyl ester (77.1 g, 77% yield).

1. temperaturecooled with ice-water bath
2. waitat room temperature for 2 h
3. extractionthe mixture was extracted with ethyl acetate (3×1 L)
4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
5. concentrationconcentrated in vacuo
6. additionThe residue was treated with hexanes/ethyl acetate (3×800 mL, hexanes/ethyl acetate=10/1
7. filtrationThe mixture was filtered
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationThe filtrate was concentrated
10. customthe crude product was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 10% ethyl acetate/hexanes)