2-Fluoroaniline → 5-Bromo-3,4-difluoro-2-((2-fluorophenyl)amino)benzoic acid

To a solution of 2-fluoroaniline (4.27 ml, 44.3 mmol) in THF (30 ml) at −78° C. was added LiHMDS (66.6 ml, 1 M in THF, 66.6 mmol) dropwise. The reaction mixture was stirred for 10 min and a solution of 5-bromo-2,3,4-trifluorobenzoic acid (5.63 g, 22.2 mmol) in THF (40 ml) was added to the mixture. The reaction was slowly warmed to room temperature and stirred at this temperature for 4 h. The mixture was concentrated, quenched with 10% HCl solution (70 ml), and extracted with EtOAc (2×200 ml). The combined organic solution was dried over MgSO4 and concentrated to dryness. Purification by trituration with boiling CH2Cl2 gave 4.40 g (57%) of 5-bromo-3,4-difluoro-2-(2-fluorophenylamino)benzoic acid as a yellow solid.

1. stirringstirred at this temperature for 4 h
2. concentrationThe mixture was concentrated
3. customquenched with 10% HCl solution (70 ml)
4. extractionextracted with EtOAc (2×200 ml)
5. dry with materialThe combined organic solution was dried over MgSO4
6. concentrationconcentrated to dryness
7. customPurification by trituration with boiling CH2Cl2

ORD record

ord-3bdeb21ec0a74b539521ee25cb34289d

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08063049B2