Acetyl chloride → 4-Chloro-3-(1-methylpiperidin-4-yl)aniline

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Reaction Steps

To a solution of 3-(1-methylpiperidin-4-yl)aniline (D6, 1.0 g, 5.3 mmol) in dichloromethane (50 ml) containing triethylarnine (1.1 ml, 7.9 mmol) was added dropwise acetyl chloride (0.40 ml, 5.6 mmol) and the mixture stirred at room temperature overnight. The mixture was washed with aqueous 10% sodium carbonate and the organics dried (Na2SO4), and evaporated in vacuo to a red semi-solid (1.49 g). To a solution of the solid in 1,2-dichloroethane (100 ml) was added N-chlorosuccinimide (1.2 g, 9.0 mmol) and the mixture heated at 80° C. for 28 h. On cooling, water (50 ml) was added and the aqueous basified with aqueous 10% sodium carbonate. The aqueous was extracted with dichloromethane (3×), the combined organics dried (Na2SO4). and evaporated in vacuo to a brown solid (650 mg). A stirred solution of the solid in ethanol (10 ml) and 2M NaOH (16 ml) was heated at reflux under argon for 18 h. The mixture was concentrated in vacuo, partitioned between ethyl acetate and water and the aqueous further extracted with ethyl acetate (3×). The combined organics were dried (Na2SO4) and evaporated in vacuo to the title compound as a pale brown solid (403 mg, 35%).

Provenance & Evidence