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

Temperature

80 °C

A two-necked, round-bottomed flask (25 cc) was charged with 5-amino-2-chloro-4-fluorophenol (1.015 g, 6.28 mmol), potassium carbonate (1.72 g, 12.4 mmol), potassium iodide (4.0 mg, 0.024 mmol) and solvent N,N-dimethylformamide (5 mL) and the mixture was stirred at 80° C. for 1 h. Subsequently, cyclopentyl bromide (1.00 g, 6.71 mmol) was added and the mixture was stirred at 80° C. for an additional 2 h. After the reaction was completed, the reaction mixture was cooled to room temperature and water (20 mL) was added, followed by extraction with toluene (20 mL×3). The organic layers were combined, washed with water (10 mL) and saturated brine (10 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 (1.43 g, 6.23 mmol; yield=99.0%). BP: 143°-145° C./1.5 mmHg 1H-NMR(CDCl3, TMS,ppm): δ1.40-2.00(8H,m), 3.72(2H,s), 4.67(1H,m), 6.39(1H,d,JHF =9.0Hz), 7.04(1H,d,JHF =11.0Hz). IR (neat, cm-1): 3500, 3400, 1630, 1510, 1420, 1245, 1185.

1. stirringthe mixture was stirred at 80° C. for an additional 2 h
2. temperaturethe reaction mixture was cooled to room temperature
3. extractionfollowed by extraction with toluene (20 mL×3)
4. washwashed with water (10 mL) and saturated brine (10 mL)
5. dry with materialdried with anhydrous magnesium sulfate
6. customAfter the desiccant was removed
7. distillationthe solvent was distilled off under vacuum

ORD record

ord-c36cc83293b949eba74d9b6fa11f8993

Source dataset

uspto-grants-1997_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05639915