反应详情

PTSA (24.7, 130 mmol) and ethylene glycol (24.8 mL, 439 mmol) were added to methyl-4-oxo-3-piperidine carboxylate hydrochloride (90) (25.1 g, 130 mmol) in benzene (52 mL, 2.5 M). The solution was stirred and heated to reflux overnight. H2O was removed using a Dean Stark trap. When the reaction was judged complete by TLC, 5% aqueous NaHCO3 and CH2Cl2 were added, and the organic layer was removed. The aqueous layer was extracted with CH2Cl2 (5×), and the combined organics were dried over sodium sulfate, filtered and concentrated in vacuo, and purified by silica gel chromatography with 20:1 CH2Cl2:2N NH3 in EtOH to provide 91 (16.7 g, 64%). 1H NMR (CDCl3) 3.82-3.70 (4H, m), 3.48 (3H, s), 3.00-2.50 (4H, m), 2.43 (1H, t), 1.76 (1H, m), 1.30 (1H, m) ppm. 13C NMR (CDCl3): 171.83, 106.57, 64.34, 64.17, 51.36, 48.91, 46.54, 43.69, 33.97 ppm.

1. temperatureheated
2. temperatureto reflux overnight
3. customH2O was removed
4. additionwere added
5. customthe organic layer was removed
6. extractionThe aqueous layer was extracted with CH2Cl2 (5×)
7. dry with materialthe combined organics were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. custompurified by silica gel chromatography with 20:1 CH2Cl2