반응 #44259

반응 방정식

Methyl 2-chloro-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate

2-fluoro-4-(methylthio)aniline

lithium bis(trimethylsilyl)amide

→

desired product

수율 77.0%

methyl 5-fluoro-2-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate

수율 77.0%

용매

THF

THF

반응 조건

후처리

1. 1
   workup.ADDITIONafter the addition
2. 2
   workup.STIRRINGthe reaction mixture was stirred for 30 minutes at −78° C
3. 3
   기타The reaction was quenched by the addition of 1 M HCl until the pH of the reaction mixture
4. 4
   workup.ADDITIONdiluted with EtOAc and saturated NaCl
5. 5
   기타The organic layer was separated
6. 6
   건조dried (Na2SO4)
7. 7
   농축concentrated under reduced pressure
8. 8
   기타Purification by flash column chromatography (methylene chloride/EtOAc, 15:1)

실험 절차

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.

출처