Hydrochloric Acid → 2-[3-(3,4-Dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)piperidin-3-yl]ethyl 4-chlorobenzenesulfonate

Participants

Reaction Conditions

Reaction Steps

To a solution of (+)-2-[3-(3,4-dichlorophenyl)piperidin-3-yl]ethanol (1.70 g, 6.20 mmol) in tetrahydrofuran (85 ml) was added triethylamine (1.30 ml, 9.35 mmol), and the resulting mixture was cooled to 0-5° C. After cooling, a solution of 3,4,5-trimethoxybenzoyl chloride (1.46 g, 6.33 mmol) in tetrahydrofuran (7 ml) was further added dropwise at below 5° C., and the resulting mixture was stirred at 0-5° C. for 5 hours and then evaporated to dryness in vacuo. Subsequently, to the residue obtained were added methylene chloride (50 ml), triethylamine (1.30 ml, 9.35 mmol) and 4-dimethylaminopyridine (0.076 g, 0.62 mmol), and the resulting mixture was cooled to 0-5° C. After cooling, a solution of 4-chlorobenzenesulfonyl chloride (1.57 g, 7.44 mmol) in methylene chloride (3.5 ml) was further added dropwise at below 5° C., and the resulting mixture was stirred at 0-5° C. for 5 hours. After completion of the reaction, water (50 ml) and concentrated hydrochloric acid (2 ml) were added to the reaction mixture, and the resulting mixture was partitioned. The separated organic layer was washed with water (50 ml) and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column and then crystallized from a mixed solvent of ethyl acetate (6.6 ml) and hexane (17.7 ml) under ice-cooling to afford the title compound [3.0 g, yield: 76.3%] as a colorless crystalline solid.

Provenance & Evidence