3-Chloro-4-fluoroaniline → 3-chloro-N-(3-chloro-4-fluorophenyl)propanamide

Participants

Reaction Conditions

Reaction Steps

A solution of 3-chloropropionyl chloride (127 g) in acetone (200 cc) is added with stirring in the course of 35 minutes to a solution, at a temperature in the region of 55°) C., of 3-chloro-4-fluoroaniline (291 g) in acetone (500 cc), and the mixture is maintained at this temperature for 2 hours. After cooling to approximately 20° C., the insoluble matter is removed by filtration and washed with acetone (2×200 cc). The combined filtrate and washings are poured with stirring into water (2 liters) and ice (1 kg). The temperature is allowed to rise to approximately 20° C. and the product is extracted with dichloromethane (4×500 cc). The combined organic extracts are washed with water (3×500 cc), dried over magnesium sulphate, stirred for 15 minutes with Norit vegetable charcoal (6 g), filtered through diatomaceous silica for filtration and concentrated under reduced pressure (2.7 kPa) at 50° C. The solid obtained is recrystallized in a mixture of cyclohexane (133 cc) and isopropyl ether (67 cc). 3'-Chloro-4'-fluoro-3-chloropropionanilide (176 g) is obtained in the form of a beige solid, m.p. 94° C., which is used without further treatment for the subsequent steps.

Provenance & Evidence