Benzoyl Peroxide → HCID 22626651, compound

Participants

Reaction Steps

3-Chlorophenylacetic acid (20.90 g, 122.51 mmol) and N-Bromosuccinimide NBS (23.50 g, 132.03 mmol) were dissolved in carbon tetrachloride (300 mL). Benzoyl peroxide BPO (300 mg) was added and the resulting reaction mixture was heated to reflux under a sunlamp for 5 hours, then cooled to room temperature, filtered and concentrated to give the desired α-bromo-3-chlorophenylacetic acid, component “A”. 10.00 g of this acid were dissolved in MeOH (100 mL) and 2 mL of sulfuric acid were added. The resulting reaction mixture was refluxed for 3 hours, and then concentrated. The residue was diluted with ether (150 mL) and washed with water, dried over sodium sulfate, and then concentrated to give the methyl ester. The methyl ester was reacted with the component “B”, 3,4-dimethylaniline (CAS 95-64-7) (6.89 g, 1.5 eq), and potassium carbonate (13.00 g, 2.5 eq) in methylethyl ketone and the mixture heated with stirring at 80° C. for 14 hours. After concentration, MeOH (50 mL) was added, followed by KOH (5.00 g). The reaction mixture was refluxed for 6 hours, acidified with concentrated HCl, and then concentrated. The resulting residue was diluted with ether and washed with water, then dried over sodium sulfate and concentrated to the 2-(3-chlorophenyl)-2-((3,4-dimethylphenyl)amino)acetic acid, which was used in the next step without further purification. Crude 2-(3-chlorophenyl)-2-(3,4-dimethylphenyl)amino)acetic acid reacted with 1,1′-carbonyldiimidazole (2.40 g, 14.81 mmol) and (Z)-N′-hydroxy-2-(methylamino) nicotinimidamide (1.80, 10.83 mmol) according to the protocols as outlined in general procedure described above to afford Compound 1.

Provenance & Evidence