Water → 5-[(But-3-yn-2-yl)oxy]-4-chloro-2-fluoroaniline

Temperature

60 °C

A round-bottomed flask (50 cc) was charged with 5-amino-2-chloro-4-fluorophenol (1.40 g, 8.67 mmol), (1-butyn-3-yl)tosylate (2.03 g, 9.00 mmol) and tetrabutylammonium bromide (71 mg, 0.22 mmol) to prepare a solution in toluene (25 mL). Subsequently, 48% sodium hydroxide in aqueous solution (6 mL) was added slowly and the mixture was stirred under heating at 60° C. for 2 h. After completion of the reaction, the reaction mixture was cooled to room temperature and water (15 mL) was added, followed by extraction with toluene (10 mL×2). The organic layers were combined and washed with water (10 mL×2). The solvent was distilled off under vacuum from the resulting toluene solution, thereby giving 4-chloro-2-fluoro-5-{(1-butyn-3-yl)oxy}aniline (1.04 g, 4.87 mmol; yield=56.1%). MP: 74.5°-75.5° C. 1H-NMR(CDCl3,TMS,ppm): δ1.60(3H,d,J=6.3Hz), 2.48(1H, d,J=1.5Hz), 3.46(2H,brs), 4.72(1H,d&q,J=6.3 and 1.5Hz), 6.62(1H,d,JHF =7.5Hz), 7.01(1H, d,JHF =10.0Hz).

1. customAfter completion of the reaction
2. temperaturethe reaction mixture was cooled to room temperature
3. extractionfollowed by extraction with toluene (10 mL×2)
4. washwashed with water (10 mL×2)
5. distillationThe solvent was distilled off under vacuum from the resulting toluene solution

ORD record

ord-239ef32d223b4484999f486f9bfd8b1c

Source dataset

uspto-grants-1997_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05639915