2,2-dimethylpropanedioyl dichloride

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

Procedure: To a 500 ml. one-necked flask equipped with reflux condenser with drying tube, is added 50 grams (0.38 mole) dimethylmalonic acid (Aldrich Chemical Co.) and 300 ml. thionyl chloride. The mixture is heated to reflux for about 1 hour during which time the dimethylmalonic acid is dissolved and hydrogen chloride and sulfur dioxide are evolved. The unreacted thionyl chloride is removed by distillation under reduced pressure. The residue is recrystallized twice from cyclohexane to yield a white solid, M.P. 186°-187° C. one-necked flask equipped with reflux condenser with drying tube The mixture is heated is dissolved The unreacted thionyl chloride is removed by distillation under reduced pressure The residue is recrystallized twice from cyclohexane to yield a white solid, M.P. 186°-187° C.

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

Procedure: To a 500 ml. one-necked flask equipped with reflux condenser with drying tube, is added 50 grams (0.38 mole) dimethylmalonic acid (Aldrich Chemical Co.) and 300 ml. thionyl chloride. The mixture is heated to reflux for about 1 hour during which time the dimethylmalonic acid is dissolved and hydrogen chloride and sulfur dioxide are evolved. The unreacted thionyl chloride is removed by distillation under reduced pressure. The residue is recrystallized twice from cyclohexane to yield a white solid, M.P. 186°-187° C. one-necked flask equipped with reflux condenser with drying tube The mixture is heated is dissolved The unreacted thionyl chloride is removed by distillation under reduced pressure The residue is recrystallized twice from cyclohexane to yield a white solid, M.P. 186°-187° C.

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

Procedure: To a 500 ml. one-necked flask equipped with reflux condenser with drying tube, is added 50 grams (0.38 mole) dimethylmalonic acid (Aldrich Chemical Co.) and 300 ml. thionyl chloride. The mixture is heated to reflux for about 1 hour during which time the dimethylmalonic acid is dissolved and hydrogen chloride and sulfur dioxide are evolved. The unreacted thionyl chloride is removed by distillation under reduced pressure. The residue is recrystallized twice from cyclohexane to yield a white solid, M.P. 186°-187° C. one-necked flask equipped with reflux condenser with drying tube The mixture is heated is dissolved The unreacted thionyl chloride is removed by distillation under reduced pressure The residue is recrystallized twice from cyclohexane to yield a white solid, M.P. 186°-187° C.

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

Procedure: Under ice cooling, a N,N-dimethylacetamide (3 mL) solution of dimethylmalonic acid dichloride (0.68 g, 4.0 mmol) was added dropwise to a N,N-dimethyl acetamide (5 mL) suspension of 5-benzyloxy-N1-methylbenzene-1,2-diamine ½ sulfate (1.11 g, 4.0 mmol). After the reaction solution was stirred at the same temperature for 4 hours, water (8 mL) was added. The mixture was stirred at 10° C. or less for 30 minutes, and precipitated crystals were collected by filtration. The resulting crystals were washed with water, and dried at 60° C., thereby obtaining 0.75 g of a slightly pink, powdery target compound (yield: 57.8%). The mixture was stirred at 10° C. or less for 30 minutes precipitated crystals were collected by filtration The resulting crystals were washed with water dried at 60° C.

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

Procedure: Under ice cooling, dimethylmalonic acid dichloride (9.9 mL, 74.9 mmol) was added dropwise to a N,N-dimethyl acetamide (90 mL) solution of 5-benzyloxy-N1-methylbenzene-1,2-diamine hydrochloride (18.0 g, 68.0 mmol). The mixture was stirred at the same temperature for 2.5 hours, and water (90 mL) was added thereto. The reaction solution was stirred at 10° C. or less for 30 minutes, and precipitated crystals were collected by filtration. The resulting crystals were washed with water, then added to methanol (180 mL), and heated under reflux. The mixture was cooled and stirred at 10° C. or less for 30 minutes, and precipitated crystals were collected by filtration. The resulting crystals were washed with methanol (36 mL), and dried at 60° C., thereby obtaining 18.3 g of a white, powdery target compound (yield: 83%). The reaction solution was stirred at 10° C. or less for 30 minutes precipitated crystals were collected by filtration The resulting crystals were washed with water added to methanol (180 mL) heated under reflux The mixture was cooled stirred at 10° C. or less for 30 minutes precipitated crystals were collected by filtration The resulting crystals were washed with methanol (36 mL) dried at 60° C.

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

Procedure: To a solution of 2 g (12 mmol) of dimethylmalonyl chloride in 19 ml of methylene chloride, a solution of 2 g (10 mmol) of 4-hydroxybenzophenone in 10 ml of pyridine was added over 15 min at -5° C. The mixture was stirred at 0° C. for 0.5 h, allowed to warm to 25° C. over 1 h, then stripped of the solvent, and finally stirred with 1:1 ethyl acetate-water for 1.5 h at 25° C. The organic phase was washed with cold 2% hydrochloric acid, then with water, and finally extracted with 5% sodium bicarbonate solution. The aqueous extract was acidified to pH 3 and filtered to collect crude product, which was purified by recrystallization from EtOH-water to yield the title compound. 0.325 g (10%); M.P.~147°-150° C. to warm to 25° C. over 1 h The organic phase was washed with cold 2% hydrochloric acid with water, and finally extracted with 5% sodium bicarbonate solution The aqueous extract filtered to collect crude product, which was purified by recrystallization from EtOH-water

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

Procedure: To a solution of 2 g (12 mmol) of dimethylmalonyl chloride in 19 ml of methylene chloride, a solution of 2 g (10 mmol) of 4-hydroxybenzophenone in 10 ml of pyridine was added over 15 min at -5° C. The mixture was stirred at 0° C. for 0.5 h, allowed to warm to 25° C. over 1 h, then stripped of the solvent, and finally stirred with 1:1 ethyl acetate-water for 1.5 h at 25° C. The organic phase was washed with cold 2% hydrochloric acid, then with water, and finally extracted with 5% sodium bicarbonate solution. The aqueous extract was acidified to pH 3 and filtered to collect crude product, which was purified by recrystallization from EtOH-water to yield the title compound. 0.325 g (10%); M.P.~147°-150° C. to warm to 25° C. over 1 h The organic phase was washed with cold 2% hydrochloric acid with water, and finally extracted with 5% sodium bicarbonate solution The aqueous extract filtered to collect crude product, which was purified by recrystallization from EtOH-water

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 1.5 g of (S)-1-amino-1-(2-naphthyl)-2-methyl-2-propanol, 0.84 g of triethylamine (dehydrated), and 13 mL of dichloromethane (dehydrated) were mixed and then cooled to an inner temperature of −10° C. 0.6 g of dimethylmalonic acid dichloride was added dropwise thereto over 3 minutes. The resulting mixture was warmed to room temperature. The mixture was stirred as such for 7 hours to effect reaction. After completion of the reaction, 20 mL of an aqueous saturated ammonium chloride solution was added thereto to separate into layers. The organic layer obtained was washed three times with 25 mL of water and concentrated. The concentrated residue was dried under reduced pressure at an inner temperature of 40° C. to obtain 1.8 g of N,N′-bis[(1S)-(2-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-dimethylpropane-1,3-diamide (yield: 100%). The resulting mixture was warmed to room temperature reaction was added to separate into layers The organic layer obtained was washed three times with 25 mL of water concentrated The concentrated residue was dried under reduced pressure at an inner temperature of 40° C.

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 1.5 g of (S)-1-amino-1-(2-naphthyl)-2-methyl-2-propanol, 0.84 g of triethylamine (dehydrated), and 13 mL of dichloromethane (dehydrated) were mixed and then cooled to an inner temperature of −10° C. 0.6 g of dimethylmalonic acid dichloride was added dropwise thereto over 3 minutes. The resulting mixture was warmed to room temperature. The mixture was stirred as such for 7 hours to effect reaction. After completion of the reaction, 20 mL of an aqueous saturated ammonium chloride solution was added thereto to separate into layers. The organic layer obtained was washed three times with 25 mL of water and concentrated. The concentrated residue was dried under reduced pressure at an inner temperature of 40° C. to obtain 1.8 g of N,N′-bis[(1S)-(2-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-dimethylpropane-1,3-diamide (yield: 100%). The resulting mixture was warmed to room temperature reaction was added to separate into layers The organic layer obtained was washed three times with 25 mL of water concentrated The concentrated residue was dried under reduced pressure at an inner temperature of 40° C.

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 1.5 g of (S)-1-amino-1-(2-naphthyl)-2-methyl-2-propanol, 0.84 g of triethylamine (dehydrated), and 13 mL of dichloromethane (dehydrated) were mixed and then cooled to an inner temperature of −10° C. 0.6 g of dimethylmalonic acid dichloride was added dropwise thereto over 3 minutes. The resulting mixture was warmed to room temperature. The mixture was stirred as such for 7 hours to effect reaction. After completion of the reaction, 20 mL of an aqueous saturated ammonium chloride solution was added thereto to separate into layers. The organic layer obtained was washed three times with 25 mL of water and concentrated. The concentrated residue was dried under reduced pressure at an inner temperature of 40° C. to obtain 1.8 g of N,N′-bis[(1S)-(2-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-dimethylpropane-1,3-diamide (yield: 100%). The resulting mixture was warmed to room temperature reaction was added to separate into layers The organic layer obtained was washed three times with 25 mL of water concentrated The concentrated residue was dried under reduced pressure at an inner temperature of 40° C.

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 2 g of (S)-1-amino-1-(1-naphthyl)-2-methyl-2-propanol, 1.1 g of triethylamine (dehydrated), and 17 mL of dichloromethane (dehydrated) were mixed and then cooled to an inner temperature of −10° C. 0.8 g of dimethylmalonic acid dichloride was added dropwise thereto over 3 minutes and the resulting mixture was warmed to room temperature. The mixture was stirred as such for 6 hours to effect reaction. After completion of the reaction, 20 mL of an aqueous saturated ammonium chloride solution was added thereto to separate into layers. The organic layer obtained was washed three times with 25 mL of water and concentrated. The concentrated residue was dried under reduced pressure at an inner temperature of 40° C. to obtain 2.5 g of N,N′-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-dimethylpropane-1,3-diamide (yield: 100%). the resulting mixture was warmed to room temperature reaction was added to separate into layers The organic layer obtained was washed three times with 25 mL of water concentrated The concentrated residue was dried under reduced pressure at an inner temperature of 40° C.

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 2 g of (S)-1-amino-1-(1-naphthyl)-2-methyl-2-propanol, 1.1 g of triethylamine (dehydrated), and 17 mL of dichloromethane (dehydrated) were mixed and then cooled to an inner temperature of −10° C. 0.8 g of dimethylmalonic acid dichloride was added dropwise thereto over 3 minutes and the resulting mixture was warmed to room temperature. The mixture was stirred as such for 6 hours to effect reaction. After completion of the reaction, 20 mL of an aqueous saturated ammonium chloride solution was added thereto to separate into layers. The organic layer obtained was washed three times with 25 mL of water and concentrated. The concentrated residue was dried under reduced pressure at an inner temperature of 40° C. to obtain 2.5 g of N,N′-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-dimethylpropane-1,3-diamide (yield: 100%). the resulting mixture was warmed to room temperature reaction was added to separate into layers The organic layer obtained was washed three times with 25 mL of water concentrated The concentrated residue was dried under reduced pressure at an inner temperature of 40° C.