docosanoyl 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:; See reaction.notes.procedure_details.

Procedure: A mixture of docosanoic acid (500 mg) and thionyl chloride (2 ml) in benzene (5 ml) was refluxed for 1 hour. After removal of the solvent under reduced pressure, the residue was taken up in benzene and benzene was evaporated off. This operation was repeated three times to give crude docosanoyl chloride. Meanwhile, a solution of dibenzyl N-(N-tert-butoxycarbonyl-L-valyl)-L-glutamate (773 mg) and anisole (0.25 ml) in trifluoroacetic acid (1 ml) was stirred at 0° C. for 1 hour. Evaporation of trifluoroacetic acid under reduced pressure gave a residue which was taken up in benzene. Benzene was distilled off by using a high vacuum pump. This operation was repeated three times to leave crude dibenzyl N-(L-valyl)-L-glutamate, which was dissolved in tetrahydrofuran (5 ml). To this solution were added triethylamine (0.7 ml) and a solution of docosanoyl chloride prepared as mentioned above in tetrahydrofuran (3 ml). After the resulting mixture was stirred at room temperature for 3 hours, the solvent was removed under reduced pressure, and the residue was dissolved in chloroform. The chloroform solution was washed with 1N sodium hydroxide solution, 1N hydrochloric acid solution, and an aqueous solution of sodium bicarbonate successively, and then dried over magnesium sulfate. After evaporation of the solvent, the residue was purified by being subjected to a silica gel column chromatography. Elution with chloroform and an usual work-up afforded dibenzyl N-(N-docosanoyl-L-valyl)-L-glutamate (520 mg, powder). was refluxed for 1 hour After removal of the solvent under reduced pressure benzene was evaporated off to give crude docosanoyl chloride Evaporation of trifluoroacetic acid under reduced pressure gave a residue which Benzene was distilled off to leave crude dibenzyl N-(L-valyl)-L-glutamate, which the solvent was removed under reduced pressure the residue was dissolved in chloroform The chloroform solution was washed with 1N sodium hydroxide solution, 1N hydrochloric acid solution an aqueous solution of sodium bicarbonate successively, and then dried over magnesium sulfate After evaporation of the solvent the residue was purified Elution with chloroform

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

Procedure: N-Methyl glucamine (1.95 g, 10.0 mmol) was dissolved in 10 mL of 1.00 N sodium hydroxide solution and 10 mL of tetrahydrofuran. Docosanoyl chloride (3.58 g, 10.0 mmol) was then added to the rapidly stirred solution followed by another 20 mL portion of tetrahydrofuran. After stirring for 60 min, the thick reaction mixture was placed on a rotary evaporator and tetrahydrofuran was removed under reduced pressure. The resulting thick slurry was filtered, washed with water and dried with suction to give a waxy white solid. Chromatography (SiO2, 15%-30% MeOH/CHCl3) yielded 1.52 g of the following compound as a waxy solid. the thick reaction mixture was placed on a rotary evaporator and tetrahydrofuran was removed under reduced pressure The resulting thick slurry was filtered washed with water dried with suction to give a waxy white solid

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

Procedure: The procedure of Example 1 is repeated except that 2,6-di-t-butylhydroquinone and docosanoyl chloride were employed to yield the above named product. It has a melting point of 59°-61°C. to yield the above named product

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

Procedure: A mixture of docosanoic acid (500 mg) and thionyl chloride (2 ml) in benzene (5 ml) was refluxed for 1 hour. After removal of the solvent under reduced pressure, the residue was taken up in benzene and benzene was evaporated off. This operation was repeated three times to give crude docosanoyl chloride. Meanwhile, a solution of dibenzyl N-(N-tert-butoxycarbonyl-L-valyl)-L-glutamate (773 mg) and anisole (0.25 ml) in trifluoroacetic acid (1 ml) was stirred at 0° C. for 1 hour. Evaporation of trifluoroacetic acid under reduced pressure gave a residue which was taken up in benzene. Benzene was distilled off by using a high vacuum pump. This operation was repeated three times to leave crude dibenzyl N-(L-valyl)-L-glutamate, which was dissolved in tetrahydrofuran (5 ml). To this solution were added triethylamine (0.7 ml) and a solution of docosanoyl chloride prepared as mentioned above in tetrahydrofuran (3 ml). After the resulting mixture was stirred at room temperature for 3 hours, the solvent was removed under reduced pressure, and the residue was dissolved in chloroform. The chloroform solution was washed with 1N sodium hydroxide solution, 1N hydrochloric acid solution, and an aqueous solution of sodium bicarbonate successively, and then dried over magnesium sulfate. After evaporation of the solvent, the residue was purified by being subjected to a silica gel column chromatography. Elution with chloroform and an usual work-up afforded dibenzyl N-(N-docosanoyl-L-valyl)-L-glutamate (520 mg, powder). was refluxed for 1 hour After removal of the solvent under reduced pressure benzene was evaporated off to give crude docosanoyl chloride Evaporation of trifluoroacetic acid under reduced pressure gave a residue which Benzene was distilled off to leave crude dibenzyl N-(L-valyl)-L-glutamate, which the solvent was removed under reduced pressure the residue was dissolved in chloroform The chloroform solution was washed with 1N sodium hydroxide solution, 1N hydrochloric acid solution an aqueous solution of sodium bicarbonate successively, and then dried over magnesium sulfate After evaporation of the solvent the residue was purified Elution with chloroform

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: In a dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, a thermometer, a nitrogen inlet tube and the dropping funnel containing the docosanoyl chloride solution, 12.59 g (96 mmol) of creatine is suspended, with stirring, in 100 ml of dry dichloromethane. To this suspension a catalytic amount (0.1 mmol) of pyridine is also added. The suspension is stirred in a dry ice and acetone bath to a temperature of between about −15° C. and 0° C. When the target temperature is reached the drop wise addition of docosanoyl chloride is commenced. Addition of docosanoyl chloride continues, with cooling and stirring, until all of the docosanoyl chloride is added, after which the reaction is allowed to warm to room temperature with constant stirring. The solution is then filtered to remove any remaining creatine, and the volatile dichloromethane and pyridine are removed under reduced pressure yielding 2-(3-dodecanoyl-1-methylguanidino)acetic acid. In a dry 3-necked, round bottomed flask, equipped with a magnetic stirrer with cooling The solution is then filtered to remove any remaining creatine the volatile dichloromethane and pyridine are removed under reduced pressure

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a dry 2-necked, round bottomed flask, equipped with a magnetic stirrer and fixed with a separatory funnel, containing 7.88 ml (108 mmol) of thionyl chloride, and a water condenser, is placed 20.44 g (60 mmol) of docosanoic acid. Addition of the thionyl chloride is completed with heating to about 45° C. over the course of about 30 minutes. When addition of the thionyl chloride is complete the mixture is heated and stirred for an additional 70 minutes. The water condenser is then replaced with a distillation side arm condenser and the crude mixture is distilled. The crude distillate in the receiving flask is then fractionally distilled to obtain the acyl chloride, docosanoyl chloride. This acyl chloride, 21.60 g (60 mmol), is put into a dry separatory funnel and combined with 100 ml of dry dichloromethane for use in the next step of the reaction. In a dry 2-necked, round bottomed flask, equipped with a magnetic stirrer fixed with a separatory funnel is heated the crude mixture is distilled The crude distillate in the receiving flask is then fractionally distilled

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a dry 2-necked, round bottomed flask, equipped with a magnetic stirrer and fixed with a separatory funnel, containing 7.88 ml (108 mmol) of thionyl chloride, and a water condenser, is placed 20.44 g (60 mmol) of docosanoic acid. Addition of the thionyl chloride is completed with heating to about 45° C. over the course of about 30 minutes. When addition of the thionyl chloride is complete the mixture is heated and stirred for an additional 70 minutes. The water condenser is then replaced with a distillation side arm condenser and the crude mixture is distilled. The crude distillate in the receiving flask is then fractionally distilled to obtain the acyl chloride, docosanoyl chloride. This acyl chloride, 21.60 g (60 mmol), is put into a dry separatory funnel and combined with 100 ml of dry dichloromethane for use in the next step of the reaction. In a dry 2-necked, round bottomed flask, equipped with a magnetic stirrer fixed with a separatory funnel is heated the crude mixture is distilled The crude distillate in the receiving flask is then fractionally distilled

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

Procedure: In a three necked flask equipped with a dropping funnel, a thermometer and a reflux condenser, 138 g of p-nitroaniline was dissolved in a mixed solvent consisting of 3000 ml of tetrahydrofuran and 140 ml of pyridine while passing nitrogen gas through the flask. Then, 395 g of docosanoylchloride placed in the dropping funnel was gradually dropped into the flask over a time span of 20 minutes, while stirring the reaction mixture. After the completion of the dropping, the reaction mixture was further stirred for 2 hours. A solid reaction product was produced. The solid reaction product was collected by filtering, the filtrate was concentrated under a reduced pressure to produce crystals. The crystals were collected and recrystallized from ethyl alcohol. As a result, 405 g of 4'-nitro-n-docosaneanilide was obtained at a yield of 88%. In a three necked flask equipped with a dropping funnel was gradually dropped into the flask over a time span of 20 minutes After the completion of the dropping, the reaction mixture was further stirred for 2 hours A solid reaction product was produced The solid reaction product was collected by filtering the filtrate was concentrated under a reduced pressure to produce crystals The crystals were collected recrystallized from ethyl alcohol