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

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.

1. additionwas added dropwise
2. customto reach room temperature
3. stirringstirred for 18 hours
4. custombefore being quenched by addition of a 1M aqueous HCl (ca. 50 mL)
5. extractionextracted with ethyl acetate
6. customThe organic layer was separated
7. washwashed with water
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customevaporated in vacuo

ORD record

ord-8076f08d9b2548178ae06ce9e79964fd

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841462B2