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

To a solution of 2-fluoro-aniline (177 mmol, 17.0 ml) in THF (80 mL) at −78° C. was added LiHMDS (265 mmol, 265 ml) and stirred for 30 min. To the reaction was added a solution of 5-bromo-2,3,4-trifluorobenzoic acid (78.4 mmol, 20.1 g) in THF (60 ml) at −78° C. The reaction was warmed to room temperature and stirred at the temperature over night. The reaction is concentrated and slowly 10% HCl (180 ml) is added. The mixture was extracted with ethyl acetate (100 ml×3), dried over MgSO4 and concentrated under reduced pressure. The crude material was taken in CH2CH2 (˜250 ml) and heated up to 45° C. for 10 min. Purification by trituration with CH2Cl2 gave 11 g (72%) of the desired product as a light yellow solid.

1. stirringstirred at the temperature over night
2. concentrationThe reaction is concentrated
3. additionslowly 10% HCl (180 ml) is added
4. extractionThe mixture was extracted with ethyl acetate (100 ml×3)
5. dry with materialdried over MgSO4
6. concentrationconcentrated under reduced pressure
7. temperatureheated up to 45° C. for 10 min
8. customPurification by trituration with CH2Cl2

ORD-Eintrag

ord-cf9e890480a4466ea63d5e92edc7b591

Quelldatensatz

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08063049B2