反应详情

温度

80 °C

To a solution of 3-oxo-3-(tetrahydro-furan-3-yl)-propionic acid ethyl ester (4.0 g, 21.5 mmol) and guanidine hydrochloride (2.6 g, 27.2 mmol) in MeOH (125 mL) at 23° C. was added potassium tert-butoxide in portions (3.4 g, 30.3 mmol) over 5 min. The reaction was heated at 80° C. for 18 h. The mixture was filtered while warm to remove insoluble salts, and the filtrate was concentrated to afford an oil which was diluted with water (˜25 mL) and extracted with EtOAc (8×50 mL). The combined organic layers were washed with satd. aq. NaCl, dried, and concentrated to give a residue. The aqueous portion was concentrated to afford a solid residue that was collected and rinsed with MeOH. The residue and solid materials were combined and chromatographed (2 M NH3 in MeOH/EtOAc) to provide 2.02 g of product as a white solid (51%). MS (ESI): mass calcd. for: C8H11N3O2, 181.1; m/z found, 182.2 [M+H]+. 1H NMR (CD3OD): 5.66 (br s, 1H), 3.93-4.01 (m, 2H), 3.75-3.85 (m, 2H), 3.28-3.31 (m, 2H), 3.16-3.24 (m, 1H), 2.18-2.27 (m, 1H), 2.05-2.15 (m, 1H).

1. filtrationThe mixture was filtered
2. temperaturewhile warm
3. customto remove insoluble salts
4. concentrationthe filtrate was concentrated
5. customto afford an oil which
6. extractionextracted with EtOAc (8×50 mL)
7. washThe combined organic layers were washed with satd
8. dry with materialaq. NaCl, dried
9. concentrationconcentrated
10. customto give a residue
11. concentrationThe aqueous portion was concentrated
12. customto afford a solid residue that
13. customwas collected
14. washrinsed with MeOH
15. customchromatographed (2 M NH3 in MeOH/EtOAc)