2-(4-chlorophenoxy)-2-methylpropanoyl chloride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 2-(4-chlorophenoxy)-2-methylpropionic acid (15.0 g) and thionyl chloride (70 ml) was boiled under reflux for 1 hour. The thionyl chloride was distilled off and the residue distilled under vacuum to give 2-(4-chlorophenoxy)-2-methylpropionyl chloride, b.p. 84-87° C. at 0.07 mbar. A solution of this chloride (14.17 g) in dichloromethane (50 ml) was added dropwise to a mixture of 1-(3-aminopropyl)imidazole (7.63 g), triethylamine (6.78 g) and dichloromethane (100 ml) at below 0° C. with stirring. After the addition, the mixtures was allowed to warm up to ambient temperature and stirred at this temperature for 2 hours. Saturated aqueous sodium bicarbonate solution (100 ml) was added and the mixture stirred for 1 hour. The mixture was separated and the aqueous layer was washed with dichloromethane. The combined organic layers were dried and evaporated to give a solid which was recrystallised from ethyl acetate to give 2-(4-chlorophenoxy)-N-[3-(imidazol-1-yl)propyl]-2-methylpropionamide, m.p. 83-84° C. under reflux for 1 hour The thionyl chloride was distilled off the residue distilled under vacuum

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

Procedure: A mixture of 2-(4-chlorophenoxy)-2-methylpropionic acid (15.0 g) and thionyl chloride (70 ml) was boiled under reflux for 1 hour. The thionyl chloride was distilled off and the residue distilled under vacuum to give 2- (4-chlorophenoxy) -2-methylpropionyl chloride, b.p. 84-87° C. at 0.07 mbar. A solution of this chloride (14.17 g) in dichloromethane (50 ml) was added dropwise to a mixture of 1-(3-aminopropyl)imidazole (7.63 g), triethylamine (6.78 g) and dichloromethane (100 ml) at below 0° C. with stirring. After the addition, the mixture was allowed to warm up to ambient temperature and stirred at this temperature for 2 hours. Saturated aqueous sodium bicarbonate solution (100 ml) was added and the mixture stirred for 1 hour. The mixture was separated and the aqueous layer was washed with dichloromethane. The combined organic layers were dried and evaporated to give a solid which was recrystallised from ethyl acetate to give 2-(4-chlorophenoxy)-N-[3-(imidazol-1-yl)propyl ]-2-methylpropionamide, m.p. 83-84° C. under reflux for 1 hour The thionyl chloride was distilled off the residue distilled under vacuum

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An amount of 10.6 g (86 mmol) of trimethyl phosphite was added dropwise to 20.0 g (86 mmol) of p-chlorophenoxyisobutyryl chloride cooled to 0° C. As varification of the reaction, evolution of methyl chloride could be observed. Distillation under reduced pressure gave 19.0 g (62 mmol) of dimethyl p-chlorophenoxyisobutyrylphosphonate as an almost colorless oil. Distillation under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.17 g (5 mmoles) of 5,5-dimethyl-2-phenylthiazolidine-4(S)-carboxylic acid and 0.7 ml of triethylamine are dissolved in 20 ml of dichloromethane while stirring and the solution is cooled to 0° C. Then, 2-(4-chlorophenoxy)-isobutyryl chloride dissolved in 4 ml of dichloromethane is added under stirring. After stirring for 3 hours, the solution is washed with water, dried over anhydrous magnesium sulphate and evaporated. The obtained syrup is recrystallized from methanol by adding water to give the title compound in a yield of 1.39 g (64%), m.p.: 177°-181° C., [α]D21 =0° (c=0.94, dimethylsulphoxide). is added under stirring After stirring for 3 hours the solution is washed with water dried over anhydrous magnesium sulphate evaporated The obtained syrup is recrystallized from methanol by adding water

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.17 g (5 mmoles) of 5,5-dimethyl-2-phenylthiazolidine-4(S)-carboxylic acid and 0.7 ml of triethylamine are dissolved in 20 ml of dichloromethane while stirring and the solution is cooled to 0° C. Then, 2-(4-chlorophenoxy)-isobutyryl chloride dissolved in 4 ml of dichloromethane is added under stirring. After stirring for 3 hours, the solution is washed with water, dried over anhydrous magnesium sulphate and evaporated. The obtained syrup is recrystallized from methanol by adding water to give the title compound in a yield of 1.39 g (64%), m.p.: 177°-181° C., [α]D21 =0° (c=0.94, dimethylsulphoxide). is added under stirring After stirring for 3 hours the solution is washed with water dried over anhydrous magnesium sulphate evaporated The obtained syrup is recrystallized from methanol by adding water

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

Procedure: Metoclopramide (59.8 g.; 0.2 mole) and triethylamine (30.0 g; 0.3 mole) are dissolved in 400 ml. of chloroform. To this mixture there is added dropwise 2-(4-chlorphenoxy)-2-methylpropionic acid chloride (72.0 g.; 0.3 mole). The mixture is heated under reflux for two hours and is subsequently mixed with 100 ml. of 20% caustic soda solution and with water. After evaporation, the distillation residue is recrystallized from methanol whereby 73.2 g. (73.7% of theory) of 4-[2-(4-chlorphenoxy)isobutyroylamino]-5-chloro-2-methoxy-N-[2-(diethylamino)-ethyl]benzamide having a melting point of 120°-121° C. is obtained. The mixture is heated under reflux for two hours is subsequently mixed with 100 ml After evaporation the distillation residue is recrystallized from methanol whereby 73.2 g

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

Procedure: Metoclopramide (59.8 g.; 0.2 mole) and triethylamine (30.0 g; 0.3 mole) are dissolved in 400 ml. of chloroform. To this mixture there is added dropwise 2-(4-chlorphenoxy)-2-methylpropionic acid chloride (72.0 g.; 0.3 mole). The mixture is heated under reflux for two hours and is subsequently mixed with 100 ml. of 20% caustic soda solution and with water. After evaporation, the distillation residue is recrystallized from methanol whereby 73.2 g. (73.7% of theory) of 4-[2-(4-chlorphenoxy)isobutyroylamino]-5-chloro-2-methoxy-N-[2-(diethylamino)-ethyl]benzamide having a melting point of 120°-121° C. is obtained. The mixture is heated under reflux for two hours is subsequently mixed with 100 ml After evaporation the distillation residue is recrystallized from methanol whereby 73.2 g