반응 #44216

반응 방정식

2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester

4-bromo-2-fluorophenylamine

lithium bis(trimethylsilyl)amide

2-Chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester

→

pure desired product

수율 65.0%

2-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid

수율 65.0%

용매

THF

THF

반응 조건

후처리

1. 1
   workup.STIRRINGthe reaction mixture was stirred for one hour at −78° C
2. 2
   기타The reaction mixture was quenched by the addition of H2O
3. 3
   workup.ADDITIONdiluted with EtOAc
4. 4
   기타The organic layer was separated
5. 5
   세척washed with saturated NaCl
6. 6
   건조dried (Na2SO4)
7. 7
   농축concentrated under reduced pressure
8. 8
   기타Purification by flash column chromatography (methylene chloride/EtOAc, 15:1)

실험 절차

Preparation of 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester: To a solution of 4-bromo-2-fluorophenylamine (0.192 g, 1.01 mmol) in THF (5 mL) at −78° C. under N2 was added lithium bis(trimethylsilyl)amide (1.50 mL, 1.50 mmol, 1 M solution in hexanes) dropwise. The reaction mixture was stirred for one hour at −78° C. 2-Chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester (0.202 g, 1.00 mmol) was then added dropwise as a solution in THF (5 mL) and the reaction mixture was stirred for one hour at −78° C. The reaction mixture was quenched by the addition of H2O and the pH was adjusted to pH 7 with saturated NH4Cl and then diluted with EtOAc. The organic layer was separated and washed with saturated NaCl, dried (Na2SO4), and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/EtOAc, 15:1) gave 0.232 g (65%) pure desired product as a white crystalline solid.

출처