反应详情

To a suspension of NaH (6.66 g, 166.5 mmol) in ether (500 mL) add methyl glycolate (15.0 g, 166.5 mmol) drop wise. Stir the reaction until evolution of H2 gas ceases. Concentrate and dissolve the solid in DMSO (300 mL). Cool the reaction to 0° C. and add methyl acrylate (16.6 mL, 183.17 mmol) drop wise. Warm the reaction to room temperature and stir overnight. Acidify the reaction with 10% HCl and extract with ether (3×). Combine organic extracts and wash with brine. Dry the organic solution (Na2SO4), filter, and concentrate in vacuo. Purify by flash chromatography (250 g SiO2, 40 mL/min, 0-50% ethyl acetate/hexane for 20 minutes and then 50% ethyl acetate/hexane for 13 minutes) to yield 4-oxo-tetrahydro-furan-3-carboxylic acid methyl ester 4a (12.9 g, 89.2 mmol, 54%) as a colorless oil. 1H NMR (δ, 400 MHz, CDCl3): 4.50 (dd, 1H, J=8.4, 9.6 Hz), 4.46 (dd, 1H, J=8.4, 9.6 Hz), 4.05 (d, 1H, J=16.8 Hz), 3.79, (s, 3H), 3.97 (d, 1H, J=16.8, Hz), 3.54 (t, 1H, J=8.4 Hz). MS calcd. 144; found (EI) 144.

1. customthe reaction until evolution of H2 gas ceases
2. concentrationConcentrate
3. dissolutiondissolve the solid in DMSO (300 mL)
4. temperatureCool
5. customthe reaction to 0° C.
6. temperatureWarm
7. customthe reaction to room temperature
8. stirringstir overnight
9. extractionextract with ether (3×)
10. washCombine organic extracts and wash with brine
11. dry with materialDry the organic solution (Na2SO4)
12. filtrationfilter
13. concentrationconcentrate in vacuo
14. customPurify by flash chromatography (250 g SiO2, 40 mL/min, 0-50% ethyl acetate/hexane for 20 minutes