Bromocyclopentane → 4-Chloro-5-(cyclopentyloxy)-2-fluorobenzenamine

Participants

Reaction Steps

A three-necked flask (2,000 cc) equipped with a mechanical stirrer was charged with 5-amino-2-chloro-4-fluorophenol (75.0 g, 0.464 mol), cyclopentyl bromide (76.3 g, 0.512 mol), tetrabutylammonium bromide (3.03 g, 9.41 mmol) and potassium iodide (776 mg, 4.67 mmol) to prepare a solution in toluene (500 mL). Subsequently, 40% sodium hydroxide in aqueous solution (500 mL) was added slowly and the mixture was stirred under heating at 80° C. (in water bath at 85°-90° C.) for 7 h. After completion of the reaction, the reaction mixture was cooled to room temperature and water (500 mL) was added, followed by extraction with toluene (400 mL×2). The organic layers were combined, washed with water (100 mL) and saturated brine (100 mL) and dried with anhydrous magnesium sulfate. After the desiccant was removed, the solvent was distilled off under vacuum to give 4-chloro-5-cyclopentyloxy-2-fluoroaniline (87.2 g, 0.380 mol; yield=81.8%).

Provenance & Evidence