Water → 2-Bromo-4-fluoro-6-methylaniline

A solution of N-bromosuccinimide (18.7 g, 0.105 mol) in 70 mL of N,N-dimethylformamide was added dropwise to a solution of 4-fluoro-2-methylaniline in 70 mL of N,N-dimethylformamide at 20° C. The reaction mixture was stirred overnight. The dark solution was poured into a mixture of water (1000 mL), brine (50 mL) and ethyl acetate (300 mL). The mixture was transferred into a separatory funnel, shacked and separated. The aqueous phase was extracted with ethyl acetate (4×150 mL). The combined organic layers were washed with water (5×100 mL), brine (2×100 mL), dried with sodium sulfate, filtered and concentrated. The 1H NMR spectrum of the crude material showed at least 95% purity. The product was further purified on silica gel pad (eluent system ethyl acetate/n-hexane: 1/8). The pure fractions were combined and evaporated to give 14.9 g of product. The impure fractions were combined, concentrated, redissolved in diethyl ether (30 mL) and extracted with 5% hydrochloric acid (5×10 mL). The acidic phase was basified with aq. potassium hydroxide and extracted with diethyl ether to provide 0.8 g of the title compound. Total yield was 15.7 g (77%).

1. customThe mixture was transferred into a separatory funnel
2. customseparated
3. extractionThe aqueous phase was extracted with ethyl acetate (4×150 mL)
4. washThe combined organic layers were washed with water (5×100 mL), brine (2×100 mL)
5. dry with materialdried with sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe product was further purified on silica gel pad (eluent system ethyl acetate/n-hexane: 1/8)
9. customevaporated

ORD record

ord-c552d2938ba74be4a39bacdf1eb01a30

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765972B2