反应详情

温度

50 °C

To a solution of 1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (7.95 g) in N,N-dimethylformamide (385 ml) was added 1,1′-carbonyldiimidazole (8.42 g). The mixture was stirred at 50° C. for 70 min. The mixture was cooled to −10° C. and (2-chloro-5-methoxy-phenyl)-acetic acid methyl ester (10.61 g) was added. Sodium hydride (60% dispersion in mineral oil, 6.59 g) was added portionwise over 30 min. The mixture was slowly warmed to room temperature and stirred for 6 h. The mixture was poured into ice water (800 ml) and saturated aqueous ammonium chloride solution (250 ml) and was extracted with ethyl acetate (5×). The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to dryness. The residue was dissolved in dimethylsulfoxide (100 ml). NaCl (3.15 g) and water (1.32 ml) were added and the mixture was heated to 140° C. for 5 h. After cooling to room temperature, ice water was added and the mixture was extracted with ethyl acetate. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to dryness to give a light brown solid. The solid was washed with cyclohexane and a small amount of dichloromethane to give the title compound as a colorless solid. More product could be obtained by chromatographic purification of the mother liquor ((SiO2, cyclohexane/EtOAc 7:3=>EtOAc). Colorless solid (9.37 g). MS (m/e)=292.1 [M+H+].

1. temperatureThe mixture was cooled to −10° C.
2. temperatureThe mixture was slowly warmed to room temperature
3. stirringstirred for 6 h
4. extractionwas extracted with ethyl acetate (5×)
5. washThe organic phase was washed with brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated to dryness
9. dissolutionThe residue was dissolved in dimethylsulfoxide (100 ml)
10. additionNaCl (3.15 g) and water (1.32 ml) were added
11. temperaturethe mixture was heated to 140° C. for 5 h
12. temperatureAfter cooling to room temperature
13. additionice water was added
14. extractionthe mixture was extracted with ethyl acetate
15. washThe organic phase was washed with brine
16. dry with materialdried (MgSO4)
17. filtrationfiltered
18. concentrationconcentrated to dryness
19. customto give a light brown solid
20. washThe solid was washed with cyclohexane