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-fluoroaniline (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. Methyl 2-chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate (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-0456192a69e843a3a707b1c622c11a17

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07732616B2