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

Participants

Reaction Conditions

Reaction Steps

A three-necked flask (500 cc) equipped with a mechanical stirrer was charged with 5-amino-2-chloro-4-fluorophenol (10.0 g, 61.9 mmol), cyclopentyl methanesulfonate (10.3 g, 62.9 mmol) and tetrabutylammonium bromide (0.51 g, 1.58 mmol) to prepare a solution in toluene (50 mL). Subsequently, 48% sodium hydroxide in aqueous solution (30 mL) was added slowly and the mixture was stirred under heating at 80° C. for 2 h. After completion of the reaction, the reaction mixture was cooled to room temperature and water (150 mL) was added, followed by extraction with toluene (50 mL×2). The organic layers were combined, washed with water (100 mL×2) and placed under vacuum to distil off the solvent, thereby giving 4-chloro-5-cyclopentyloxy-2-fluoroaniline (13.5 g, 59.0 mmol; yield=95.2%; purity on HPLC=98.6%).

Provenance & Evidence