反应详情

(S)-2-(4-Fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one (95 mg, 0.50 mmol) was dissolved in THF and cooled to −40° C. n-BuLi (1.1 eq, 0.34 ml of 2.5M solution) was added dropwise, forming a purple suspension. The mixture was allowed to stir for 30 minutes until the purple color changed to white. 1-Fluoro-2-isocyanato-4-methoxy-5-methyl-benzene (1 eq, 90 mg) was added. The mixture was allowed to stir for 1 hour at −40° C., then allowed to warm to room temperature and stirred for 2 hours. The reaction was quenched with saturated ammonium chloride solution. The mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography (gradient 9:1 to 1:1 hexanes/ethyl acetate) to give 2-(4-Fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid (2-fluoro-5-methoxy-4-methyl-phenyl)-amide (46 mg, 24.7%) as a foam. MS (ES+) m/z 373 (M+H).

1. additionwas added dropwise
2. customforming a purple suspension
3. stirringto stir for 1 hour at −40° C.
4. stirringstirred for 2 hours
5. customThe reaction was quenched with saturated ammonium chloride solution
6. additionThe mixture was diluted with water
7. extractionextracted with ethyl acetate
8. washThe combined organic extracts were washed with brine
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated in vacuo
11. customThe residue was purified by flash chromatography (gradient 9:1 to 1:1 hexanes/ethyl acetate)