反应详情

A solution of NaOH (1.76 g, 0.044 mol) in a few ml of water was added to hydroquinine (4.86 g, 0.040 mol) in 250 ml DMSO. The mixture was stirred under nitrogen for 20 minutes. 5-Chloro-2,3-difluoropyridine (6.0 g, 0.040 mol) was added. The reaction mixture was heated at 60°-70° C. for 3 hours, then poured over ice. Aqueous NaOh was added to pH 12 and the solid diether side-product was filtered off. The filtrate was acidified, extracted with ether, treated with Norite adsorbent, and the solvent was removed by rotary evaporation to give a yellow oil which solidified on standing and was purified by high pressure liquid chromatography (HPLC) (80% hexane/20% ethyl acetate) to give a white solid (2.5 g, 26% yield, m.p. 90°-92° C.).

1. temperatureThe reaction mixture was heated at 60°-70° C. for 3 hours
2. additionpoured over ice
3. additionAqueous NaOh was added to pH 12
4. filtrationthe solid diether side-product was filtered off
5. extractionextracted with ether
6. additiontreated with Norite adsorbent
7. customthe solvent was removed by rotary evaporation
8. customto give a yellow oil which
9. customwas purified by high pressure liquid chromatography (HPLC) (80% hexane/20% ethyl acetate)