4-Bromo-2-fluoroaniline → Methyl 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate

Temperature

-78 °C

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.

1. stirringthe reaction mixture was stirred for one hour at −78° C
2. customThe reaction mixture was quenched by the addition of H2O
3. additiondiluted with EtOAc
4. customThe organic layer was separated
5. washwashed with saturated NaCl
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated under reduced pressure
8. customPurification by flash column chromatography (methylene chloride/EtOAc, 15:1)

ORD record

ord-b8a3126a7146470ba3c55fd7bb40d9e6

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431574B2