2-butoxy-5-chlorobenzoyl chloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 12.2 g. ethyl 4-(2-aminoethyl)-phenylacetate hydrochloride in 40 ml dioxane and 40 ml acetone, there is added dropwise, after the addition of 8 ml pyridine, a solution of 12.3 g 2-butoxy-5-chlorobenzoyl chloride in 10 ml acetone. The reaction mixture is then stirred under reflux for 3 hours and thereafter evaporated in a vacuum. The residue is stirred with dilute hydrochloric acid and then with aqueous sodium bicarbonate solution, filtered with suction and washed with water. There are obtained 19 g of crude product which, after recrystallization from ethanol, with the addition of small amounts of water, gives ethyl 4-[2-(2-butoxy-5-chlorobenzamido)-ethyl]-phenylacetate; m.p. 80° C. under reflux for 3 hours evaporated in a vacuum The residue is stirred with dilute hydrochloric acid with aqueous sodium bicarbonate solution, filtered with suction washed with water There are obtained 19 g of crude product which after recrystallization from ethanol with the addition of small amounts of water

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11.5 g Ethyl 4-aminomethylphenylacetate hydrochloride (m.p. 172° C.; prepared by the catalytic hydrogenation of ethyl 4-cyanophenylacetate) are suspended in 200 ml toluene. After the addition of 13.9 ml triethylamine, there is added dropwise, while cooling, a solution of 12.4 g 2-butoxy-5-chlorobenzoyl chloride in 10 ml toluene. The reaction mixture is subsequently heated under reflux for 2 hours, while stirring. After cooling, the toluene phase is treated successively with dilute hydrochloric acid, aqueous sodium bicarbonate solution and water and then evaporated. The evaporation residue is heated on a steambath with 2 N aqueous sodium hydroxide solution and the solution then filtered. The filtrate is acidified with dilute hydrochloric acid. The precipitated 4-(2-butoxy-5-chlorobenzamidomethyl)-phenylacetic acid is reprecipitated via its sodium salt and recrystallized from ethanol. The yield is 3.9 g (20% of theory); m.p. 198° C. is added dropwise while cooling The reaction mixture is subsequently heated under reflux for 2 hours After cooling evaporated The evaporation residue is heated on a steambath with 2 N aqueous sodium hydroxide solution the solution then filtered The precipitated 4-(2-butoxy-5-chlorobenzamidomethyl)-phenylacetic acid is reprecipitated via its sodium salt recrystallized from ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11.5 g Ethyl 4-aminomethylphenylacetate hydrochloride (m.p. 172° C.; prepared by the catalytic hydrogenation of ethyl 4-cyanophenylacetate) are suspended in 200 ml toluene. After the addition of 13.9 ml triethylamine, there is added dropwise, while cooling, a solution of 12.4 g 2-butoxy-5-chlorobenzoyl chloride in 10 ml toluene. The reaction mixture is subsequently heated under reflux for 2 hours, while stirring. After cooling, the toluene phase is treated successively with dilute hydrochloric acid, aqueous sodium bicarbonate solution and water and then evaporated. The evaporation residue is heated on a steambath with 2 N aqueous sodium hydroxide solution and the solution then filtered. The filtrate is acidified with dilute hydrochloric acid. The precipitated 4-(2butoxy-5-chlorobenzamidomethyl)-phenylacetic acid is reprecipitated via its sodium salt and recrystallized from ethanol. The yield is 3.9 g. (20% of theory); m.p. 198° C. is added dropwise while cooling The reaction mixture is subsequently heated under reflux for 2 hours After cooling evaporated The evaporation residue is heated on a steambath with 2 N aqueous sodium hydroxide solution the solution then filtered The precipitated 4-(2butoxy-5-chlorobenzamidomethyl)-phenylacetic acid is reprecipitated via its sodium salt recrystallized from ethanol