反应详情

(S)-2-(4-Fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one (57 mg, 0.30 mmol) from Preparation 3 was dissolved in 10 ml of THF and cooled to −40° C. n-BuLi (1.1 eq, 0.12 ml of a 2.5 M soln) was added dropwise, forming a purple suspension. This mixture was allowed to stir for 30 minutes until the purple color changed to white. 1-Bromo-2-isocyanato-4,5-dimethoxy-benzene (1 eq, 77 mg) was added. The mixture was allowed to stir for 15 minutes at −40° C. then allowed to warm to room temperature and stir for 2 hours. The reaction was then 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, filtered and concentrated in vacuo. The residue was purified by flash chromatography (hexanes/ethyl acetate 7:3) to obtain (S)-2-(4-fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid (2-bromo-4,5-dimethoxy-phenyl)-amide (82 mg, 61%) as a brown oil. MS (ES+) m/z 449 (M+H).

1. additionwas added dropwise
2. customforming a purple suspension
3. stirringto stir for 15 minutes at −40° C.
4. stirringstir for 2 hours
5. customThe reaction was then 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. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by flash chromatography (hexanes/ethyl acetate 7:3)