Reaktion #44216

Reaktionsgleichung

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

Ausbeute 65.0%

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

Ausbeute 65.0%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle