反应详情

Under a nitrogen atmosphere, triethylamine (31.8 g, 0.315 mole) and 4-fluorobenzoyl chloride (50 g, 0.315 mole) were added simultaneously, dropwise, to a stirred and chilled solution of freshly prepared N-[[3-amino]-2-pyridinyl]glycine ethyl ester (0.33 mole) by palladium/carbon reduction of N-[[3-nitro]-2-pyridinyl]glycine ethyl ester, (75.3 g, 0.33 mole) in dry tetrahydrofuran (~800 ml). The reaction mixture was stirred at room temperature overnight and the solvent was evaporated under reduced pressure. The residue was partitioned between ethyl acetate (300 ml) and water (300 ml), the insoluble material was filtered off, the layers were separated and the aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed three times with water, dried over magnesium sulfate, treated with charcoal, filtered and evaporated to give 76.8 g of crude solid (77% yield). A 6.8-g portion of the solid was recrystallized from isopropyl alcohol and water to give 5.63 g of title compound, mp 127° -128° C.

1. stirringThe reaction mixture was stirred at room temperature overnight
2. customthe solvent was evaporated under reduced pressure
3. customThe residue was partitioned between ethyl acetate (300 ml) and water (300 ml)
4. filtrationthe insoluble material was filtered off
5. customthe layers were separated
6. extractionthe aqueous layer was extracted again with ethyl acetate
7. washThe combined organic layer was washed three times with water
8. dry with materialdried over magnesium sulfate
9. additiontreated with charcoal
10. filtrationfiltered
11. customevaporated
12. customto give 76.8 g of crude solid (77% yield)
13. customA 6.8-g portion of the solid was recrystallized from isopropyl alcohol and water