反应详情

A solution of 6-butyl-8-fluoroquinoline (for example, as prepared for Intermediate 2) (14.4 g, 70.9 mmol) in NMP (20 ml) was added to a mixture of tert-butyl-4-hydroxy-1-piperidinecarboxylate (commercially available, for example, from Aldrich) (21.6 g, 108 mmol) and sodium tert-butoxide (10.4 g, 108 mmol) in NMP (75 ml), and the resulting mixture was stirred at 140° C. for approximately 90 min and then allowed to cool overnight. The reaction mixture was treated with ammonium chloride solution and extracted with EtOAc (×2). The combined organic extracts were washed with water, dried (MgSO4), filtered and evaporated to dryness. The residue was purified by flash chromatography eluting with DCM-EtOAc (1:0 to 1:1) and then twice by Flashmaster chromatography eluting with DCM-EtOAc (1:0 to 3:1) over 40 min to give the title compound (22 g). LCMS RT=3.49 min, ES+ve m/z 385 [M+H]+

1. temperatureto cool overnight
2. extractionextracted with EtOAc (×2)
3. washThe combined organic extracts were washed with water
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. customevaporated to dryness
7. customThe residue was purified by flash chromatography
8. washeluting with DCM-EtOAc (1:0 to 1:1)
9. washtwice by Flashmaster chromatography eluting with DCM-EtOAc (1:0 to 3:1) over 40 min