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

Temperature

80 °C

A round-bottomed flask (300 cc) was charged with bis(5-amino-2-chloro-4-fluorophenyl)carbonate (10.0 g, 28.6 mmol), cyclopentyl methanesulfonate (10.1 g, 61.3 mmol) and tetrabutylammonium bromide (463 mg, 1.43 mmol) to prepare a solution in toluene (55 mL). Subsequently, 48% sodium hydroxide in aqueous solution (28 mL) was added slowly and the mixture was stirred under heating at 80° C. for 30 min. Subsequently, 48% sodium hydroxide in aqueous solution (27 mL) was added slowly over 30 min and the mixture was stirred under heating at 80° C. for an additional 1.0 h. After completion of the reaction, the reaction mixture was cooled to room temperature and water (100 mL) was added, followed by extraction with toluene (50 mL×2). The organic layers were combined and washed with water (100 mL×2). The solvent was distilled off under vacuum from the resulting toluene solution, thereby giving 4-chloro-5-cyclopentyloxy-2-fluoroaniline (12.6 g, 54.7 mmol; yield=95.4%; purity on HPLC=83.8%).

1. stirringthe mixture was stirred
2. temperatureunder heating at 80° C. for an additional 1.0 h
3. customAfter completion of the reaction
4. temperaturethe reaction mixture was cooled to room temperature
5. extractionfollowed by extraction with toluene (50 mL×2)
6. washwashed with water (100 mL×2)
7. distillationThe solvent was distilled off under vacuum from the resulting toluene solution

ORD record

ord-97398ef998744f9d90df730002b32d80

Source dataset

uspto-grants-1997_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05639915