4-Bromo-2-fluoroaniline → 7-(4-Bromo-2-fluoro-phenylamino)-benzo[d]isothiazole-6-carboxylic acid

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Reaction Steps

To a solution of 4-bromo-2-fluoro-phenylamine (1.05 g, 5.55 mmol) in anhydrous THF (20 mL) at −78° C. was added a 1.0 M solution of LHMDS in hexanes (8.3 mL, 8.3 mmol) under a nitrogen atmosphere. The reaction mixture was stirred for 10 minutes and a suspension of 7-fluoro-benzo[d]isothiazole-6-carboxylic acid (547 mg, 2.78 mmol) in anhydrous THF (20 mL) was added dropwise. The resultant mixture was stirred at −78° C. for 30 min, then allowed to reach room temperature and stirred for 18 hours before being quenched by addition of a 1M aqueous HCl (ca. 50 mL) and extracted with ethyl acetate. The organic layer was separated and washed with water followed by brine, dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0% to 10%, MeOH in DCM) to give the title compound as a brown solid (584 mg, 58%). LCMS (method B): RT=3.76 min, [M−H]−=365/367.

Provenance & Evidence