反应详情

温度

130 °C

4-[(2,4-difluorobenzyl)oxy]pyridine 1-oxide (from Step 1) (30.0 g, 0.127 mol), anhydrous potassium acetate (25 g, 0.25 mol), acetic anydride (25 g, 0.25 mol), and 10 ml acetic acid were combined in a 250-ml round-bottomed flask with overhead stirring and heated to 130° C. for 4 hours. The mixture was concentrated under vacuum, the solids dissolved in 95 ml acetonitrile; 5 ml water, filtered through charcoal and poured into 600 ml ice with stirring. The mixture was allowed to stand overnight at room temperature, then 9.62 g (30%) product collected by filtration as a medium brown solid (adequate for the next step without purification). 1H-NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 7.59 (quartet, J=9.91 Hz, 1H), 7.29 (t, J=10.36 Hz, 1H), 7.21 (d, J=8.20 Hz, 1H), 7.11 (t, J=8.48 Hz, 1H), 5.83 (m, 2H), 5.02 (s, 2H). 19F-NMR (400 MHz, DMSO-d6) δ −109.57 (quintet, J=7.66 Hz, 1F)-113.88 (quartet, J=8.93 Hz, 1F). LC/MS tr=4.29 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 254 nm, at 50° C.) ES-MS m/z 238 (M+H).

1. concentrationThe mixture was concentrated under vacuum
2. dissolutionthe solids dissolved in 95 ml acetonitrile
3. filtration5 ml water, filtered through charcoal
4. additionpoured into 600 ml ice
5. stirringwith stirring
6. filtration9.62 g (30%) product collected by filtration as a medium brown solid (adequate for the next step
7. customwithout purification)
8. customLC/MS tr=4.29 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 254 nm, at 50° C.) ES-MS m/z 238 (M+H)