反应详情

温度

60 °C

To a 1 L, 3-necked flask equipped with a mechanical stirrer charged with (2E)-2-cyano-2-[(3-fluoro-2-iodophenyl)hydrazono]-N-propylacetamide (43.9 g, 117 mmol) in anhydrous toluene (Aldrich, 600 mL) under N2 was added portion-wise aluminum chloride (Aldrich, 46.8 g, 352 mmol) over 20 minutes. The mixture was heated to 60° C. with vigorous stirring for 2 hours then cooled to ˜15° C. Ethyl acetate (30 mL) was carefully added while maintaining the internal temperature between 20-25° C. Additional ethyl acetate (900 mL) was then added, followed by careful addition of Rochelle's salt (saturated aqueous potassium sodium tartrate, 500 mL). Upon addition of the first 50 mL, the temperature rose from 20 to 36° C. The reaction was heated with stirring at 60° C. for 30 minutes. The aqueous layer contained a thick white precipitate and the organic layer slowly solubilized the brownish yellow solid. (Note: If a non-white (brown/yellow) solid still existed at the aqueous/organic interface, the hot extraction was repeated). The mixture was placed in a separatory funnel and the aqueous layer was removed. The organic layer was washed with Rochelle's salt (500 mL), washed with brine, dried over magnesium sulfate, filtered and concentrated to give 38 g slightly crude product (86.5%). Further purification by trituration with ethyl acetate/hexanes was carried out when appropriate. An analytically pure sample was obtained by recrystallization from ethyl acetate. 1H NMR (300 MHz, CDCl3) δ 8.54 (br, 1H), 7.84 (dd, J=5.3, 9.2 Hz, 1H), 7.39 (dd, J=7.0, 9.2 Hz, 1H), 3.47 (apparent q, J=7.0 Hz, 2H), 1.68 (apparent sextet, J=7.0 Hz, 2H), 1.03 (t, J=7.4 Hz, 3H). MS APCI, m/z=375 (M+H). HPLC 2.13 min.

1. customTo a 1 L, 3-necked flask equipped with a mechanical stirrer
2. temperaturethen cooled to ˜15° C
3. temperaturewhile maintaining the internal temperature between 20-25° C
4. additionUpon addition of the first 50 mL
5. customrose from 20 to 36° C
6. temperatureThe reaction was heated
7. stirringwith stirring at 60° C. for 30 minutes
8. extractionthe hot extraction
9. customThe mixture was placed in a separatory funnel
10. customthe aqueous layer was removed
11. washThe organic layer was washed with Rochelle's salt (500 mL)
12. washwashed with brine
13. dry with materialdried over magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated
16. customto give 38 g slightly crude product (86.5%)
17. customFurther purification by trituration with ethyl acetate/hexanes
18. customAn analytically pure sample was obtained by recrystallization from ethyl acetate
19. customHPLC 2.13 min.