反应详情

温度

120 °C

A solution of 4-fluoro-benzoic acid benzyl ester (720 mg, 3.13 mmol) in dioxane (10 mL) was treated with diisopropyl ethyl amine (1.64 mL, 9.39 mmol), ethyl isonipecotate (1.54 g, 9.39 mmol), a catalytic amount of DMAP and heated in a sealed tube at 120° C. for approximately 18 h. The mixture was then cooled, followed addition of another portion of ethyl isonipecotate (1.54 g, 9.39 mmol) and the mixture was reheated at 120° C. After stirring for one more day the mixture was cooled, another portion of ethyl isonipecotate (1.54 g, 9.39 mmol) was added and the mixture was heated again at 120° C. and stirred for an additional 3 day period. The mixture was then cooled and partitioned between EtOAc and water. The EtOAc layer was collected, dried over Na2SO4, filtered and concentrated and the residue was chromatographed with a silica gel column and 0-50% Et2O in hexanes gradient. The intermediate isolated from this operation was dissolved in EtOH (15 mL). Followed addition of 10% Pd/C (15 mg) and the mixture was hydrogenated under one atmosphere of hydrogen for 3.5 h. Followed filtration, the solids were washed with EtOH and the combined organic layer was evaporated to afford the product (200 mg, Yield 10%). HRMS m/z calcd for C15H19NO4 [M+H]+: 278.1387. Found: 278.1387.

1. temperatureThe mixture was then cooled
2. customwas reheated at 120° C
3. temperaturewas cooled
4. stirringstirred for an additional 3 day period
5. temperatureThe mixture was then cooled
6. custompartitioned between EtOAc and water
7. customThe EtOAc layer was collected
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customthe residue was chromatographed with a silica gel column and 0-50% Et2O in hexanes gradient
12. customThe intermediate isolated from this operation
13. filtrationFollowed filtration
14. washthe solids were washed with EtOH
15. customthe combined organic layer was evaporated