反应详情

KOtBu (1.17 g, 10.4 mmol) was added to ethylene glycol (10 mL, 179 mmol) to provide a homogeneous solution. 4-(7-fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (2.61 g, 7.89 mmol), as prepared in Example 65b, was added, and the opaque white slurry was stirred at rt for 3.5 hr. DMSO (5 mL) was then added, and the mixture stirred at 110° C. for 20 min at which point it became a homogeneous solution. The reaction was then stirred at rt overnight, at which point it became a translucent white slurry. The mixture was then diluted with 0.1M NaHCO3 and extracted with EtOAc (2×50 mL). The combined organic layers were washed with 0.1M NaHCO3 (1×100 mL), dried (Na2SO4), concentrated, and dissolved in ˜15 mL toluene. The title compound crystallized upon standing at rt, was filtered, and the crystalline filter cake washed with toluene (1×10 mL). The filter cake was dried under high vacuum at 100° C. to afford the title compound as a white powder (2.38 g, 81%). LC/MS (ESI): calc mass 373.2, found 374.2.

1. customto provide a homogeneous solution
2. additionwas added
3. stirringthe mixture stirred at 110° C. for 20 min at which point it
4. stirringThe reaction was then stirred at rt overnight, at which point it
5. extractionextracted with EtOAc (2×50 mL)
6. washThe combined organic layers were washed with 0.1M NaHCO3 (1×100 mL)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated
9. dissolutiondissolved in ˜15 mL toluene
10. customThe title compound crystallized
11. customupon standing at rt
12. filtrationwas filtered
13. washthe crystalline filter cake washed with toluene (1×10 mL)
14. customThe filter cake was dried under high vacuum at 100° C.