反应详情

温度

-78 °C

To a solution of 2-fluoro-4-(methylthio)aniline (0.236 g, 1.50 mmol) in THF (10 mL) at −78° C. under N2 was added lithium bis(trimethylsilyl)amide (3.42 ml, 3.42 mmol, 1 M solution in hexanes) dropwise. The reaction mixture was stirred for one hour at −78° C. after the addition was complete. Methyl 2-chloro-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate (0.300 g, 1.37 mmol) was then added dropwise as a solution in THF (5 mL) and the reaction mixture was stirred for 30 minutes at −78° C. The reaction was quenched by the addition of 1 M HCl until the pH of the reaction mixture was 5, and then diluted with EtOAc and saturated NaCl. The organic layer was separated, dried (Na2SO4), and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/EtOAc, 15:1) gave pure desired product (0.359 g, 75%) as a white solid.

1. additionafter the addition
2. stirringthe reaction mixture was stirred for 30 minutes at −78° C
3. customThe reaction was quenched by the addition of 1 M HCl until the pH of the reaction mixture
4. additiondiluted with EtOAc and saturated NaCl
5. customThe organic layer was separated
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated under reduced pressure
8. customPurification by flash column chromatography (methylene chloride/EtOAc, 15:1)