反应详情

温度

120 °C

Preparation 87 (N-(4-methoxyphenyl)isonicotinamide, 1 g, 4.39 mmol) was dissolved in phosphorous oxychloride (POCl3) (5 mL) then phosphorous pentachloride (913 mg, 4.39 mmol) was added. The mixture was heated at 120° C. for 4 h. The POCl3 was removed in vacuo, aminoacetaldehyde dimethyl acetal (9.5 mL, 87.8 mmol) and isopropanol (10 mL) were added, and the mixture was stirred at 23° C. for ca. 16 h. The reaction mixture was concentrated in vacuo and concentrated hydrochloric acid (36.5%, 25 mL) in isopropanol (15 mL) was added. The reaction mixture was heated at 90° C. for 24 h. After cooling to 23° C., aqueous sodium hydroxide (1N) and aqueous sodium bicarbonate were added to obtain pH=8. The mixture was extracted with methylene chloride, was dried (MgSO4), and was filtered and concentrated in vacuo. The residue was purified by silica gel chromatography with ethyl acetate/hexanes/methanol (80:20:0 to 76:19:5) to afford 811 mg (74% yield) of the title compound; diagnostic 13C NMR signals (100 MHz, CDCl3) δ 160.069, 149.952, 144.142, 137.853, 131.004, 129.882, 127.414, 124.977, 122.195, 115.114, 55.808; MS (AP/Cl) 252.4 (M+H)+.

1. additionwere added
2. concentrationThe reaction mixture was concentrated in vacuo and concentrated hydrochloric acid (36.5%, 25 mL) in isopropanol (15 mL)
3. additionwas added
4. temperatureThe reaction mixture was heated at 90° C. for 24 h
5. temperatureAfter cooling to 23° C.
6. additionaqueous sodium hydroxide (1N) and aqueous sodium bicarbonate were added
7. customto obtain pH=8
8. extractionThe mixture was extracted with methylene chloride
9. dry with materialwas dried (MgSO4)
10. filtrationwas filtered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by silica gel chromatography with ethyl acetate/hexanes/methanol (80:20:0 to 76:19:5)