N-bromobutanimide → 5-Bromo-4-fluoro-2-hydroxybenzoic acid

To a stirring solution of 4-fluoro-2-hydroxy-benzoic acid (5.58 g, 35.7 mmol) in dimethyl formamide (72 mL, 0.5 M) was added N-bromosuccinimide (7.08 g, 39.3 mmol). The mixture was allowed to stir for 24 h at room temperature. Next, the mixture was diluted with 300 mL of ethyl acetate and washed successively with water (3×330 mL) and saturated aq LiCl (4×200 mL). The organic layer was dried over Na2SO4, filtered and concentrated to afford 5-bromo-4-fluoro-2-hydroxy-benzoic acid (8.1 g, 96%) as a beige powder. Please note, the product may contain up to 20% of a dibrominated impurity which may be separated from the desired product after coupling with a benzylamine or upon methylation (Example 50): Rf 0.32 (20% methanol in dichloromethane); 1H NMR (DMSO-d6, 300 mHz) δ 8.00 (d, J=8.1 Hz, 1 H), 7.05 (d, J=10.5 Hz, 1 H).

1. washwashed successively with water (3×330 mL) and saturated aq LiCl (4×200 mL)
2. dry with materialThe organic layer was dried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated

ORD record

ord-bf66bada73214904a0901a3c916b0b55

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07189749B2