反应详情

4M HCl in 1,4-dioxan (20 mL, 80 mmol) was added to a suspension of 4-(5-ethoxy-2-fluoro-phenyl)-5,6-dimethyl-pyridine-2-carbonitrile (which may be prepared as described in Description 51) (1.87 g, 6.92 mmol) in methanol (20 mL) at ambient temperature. The stirred, yellow solution was refluxed under N2 for 9 h. The reaction was concentrated to one third the volume then poured into sat. aq. NaHCO3 (100 ml). The mixture was extracted with EtOAc (3×50 ml). The combined organic extracts were dried (Na2SO4) and evaporated to a colourless oil which solidified. This was purified by SiO2 column chromatography: the oil was dissolved in DCM (15 ml) and the solution was applied to a 100 g cartridge which was then eluted on a Biotage SP4 system with a gradient of EtOAc/iso-hexane (0-80%) to afford methyl 4-(5-ethoxy-2-fluoro-phenyl)-5,6-dimethyl-pyridine-2-carboxylate (D52);

1. temperatureThe stirred, yellow solution was refluxed under N2 for 9 h
2. concentrationThe reaction was concentrated to one third the volume
3. additionthen poured into sat. aq. NaHCO3 (100 ml)
4. extractionThe mixture was extracted with EtOAc (3×50 ml)
5. dry with materialThe combined organic extracts were dried (Na2SO4)
6. customevaporated to a colourless oil which
7. customThis was purified by SiO2 column chromatography
8. dissolutionthe oil was dissolved in DCM (15 ml)
9. washwas then eluted on a Biotage SP4 system with a gradient of EtOAc/iso-hexane (0-80%)