反应详情

温度

-20 °C

MeLi in ether (185 ml, 259 mmol) was added over one hour into the cooled (-78° C.) suspension of CuI (I) (47.5 g, 249 mmol) in ether (100 ml) and THF (300 ml). The resulting yellow suspension was slowly warmed up to -20° C. over about one hour, then cooled to -78° C. again. 2,6-pyridinedicarboxylic acid dichloride (Example 22, 19.1 g, 93.6 mmol) in THF (100 ml) was added over 30 minutes. The resulting orange-yellow suspension was stirred at temperature lower than -30° C. for 2.5 hours and then hydrolyzed with saturated NH4Cl--H2 O. After warmed up to room temperature, the color of the aqueous phase changed from light orange to blue. The mixture was filtered through Celite, and washed consecutively with ether and CH2Cl2. The organic phase was separated off. The aqueous phase was extracted consecutively with ether (2×80 ml) and CH2Cl2 (80 ml). The combined organic solutions were dried over Na2SO4, and then filtered. After removal of solvents, the residue was subjected to chromatography on a silica gel column, eluted with hexane/AcOEt (16:1), giving white or pale yellow solid. Yield: 14.2 g (93%). 1H-NMR (CDCl3): dH=8.18 (d, 3J(HH)=7.7 Hz, 2 H, H3,5), 7.96 (dd, 3J(HH)=8,2 and 7.3 Hz, 1 H, H4), 2.76 (s, 6 H, CH3). 13C-NMR (CDCl3): dC=199.17 (C=O), 152.46 (C2,6), 137.74 (C4), 124.51 (C3,5), 25.32 (CH3).

1. temperaturecooled
2. temperaturecooled to -78° C. again
3. temperatureAfter warmed up to room temperature
4. filtrationThe mixture was filtered through Celite
5. washwashed consecutively with ether and CH2Cl2
6. customThe organic phase was separated off
7. extractionThe aqueous phase was extracted consecutively with ether (2×80 ml) and CH2Cl2 (80 ml)
8. dry with materialThe combined organic solutions were dried over Na2SO4
9. filtrationfiltered
10. customAfter removal of solvents
11. washeluted with hexane/AcOEt (16:1)
12. customgiving white