反应详情

温度

80 °C

2,4-difluorobenzyl alcohol (100. g, 0.694 mol) and 4-nitropyridine N-oxide (98. g, 0.700 mol)are combined with 250 g Cs2CO3 (1.1 eq) in 2.5 L anhydrous dimethylformamide and heated to 80° C. with stirring. The reaction was followed by 19F-NMR (crude reaction mixture with external D2O reference) and complete after 40 h. The mixture was filtered hot; product crystallized out on cooling. 90.21 g (55%) of white plates were collected by filtration and washed with diethyl ether. The mother liquor was diluted with 2.5 L diethyl ether and stored in the freezer overnight, yielding a second crop 68.76 g (41%, combined yield 96%). 1H-NMR (400 MHz, DMSO-d6) δ 8.06 (m, 2H), 7.61 (quartet, J=8.45 Hz, 1H), 7.30 (t, J=10.37 Hz, 1H), 7.12, (t, J=8.45 Hz, 1H), 7.09 (d, J=5.06 Hz, 2H), 5.14 (s, 2H). 19F-NMR (400 MHz, DMSO-d6) δ −109.43 (quintet, J=7.78 Hz, 1F), −113.82 (quartet, J=9.55 Hz, 1F). LC/MS tr=3.90 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50° C.) ES-MS m/z 238 (M+H).

1. customreaction mixture with external D2O reference) and complete after 40 h
2. filtrationThe mixture was filtered hot
3. customproduct crystallized out
4. temperatureon cooling
5. filtration90.21 g (55%) of white plates were collected by filtration
6. washwashed with diethyl ether
7. additionThe mother liquor was diluted with 2.5 L diethyl ether
8. customstored in the freezer overnight
9. customyielding a second crop 68.76 g (41%, combined yield 96%)