Pentanimidic Acid Methyl Ester

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 31.72 g (250 mmol) of glycine methyl ester hydrochloride was added in a single portion to a solution of 10.13 g (250 mmol) of sodium hydroxide in 80 ml of methanol at 0° C. The temperature dropped to -10° C. The mixture was stirred for 10 minutes, during which time the temperature rose again to 0° C. 108.25 g (a 26.6 percent strength solution in toluene, 250 mmol) of methyl pentanimidate was added, and the mixture was stirred at room temperature for 3 hours. 35.64 g (about 92 percent strength, 275 mmol) of dimethylformamide dimethyl acetal then was added, during the course of 5 minutes. The reaction mixture was stirred for an additional 3 hours. 200 ml of toluene was added, and methanol and water were removed from the mixture by distillation in vacuo. Of the remaining 203.5 g, 91.68 g (corresponding to 112 mmol of methyl pentanimidate) was initially introduced at room temperature and treated with 65.09 g (416 mmol) of POCl3. The mixture was heated 15 100° C. for 1.5 hours and then 118.5 g of POCl3 /toluene was distilled off and the residue was treated with 121 ml of ethyl acetate and 408 ml of water. The pH was adjusted to 1, by addition of 18 ml of 30 percent strength sodium hydroxide solution, and the phases were separated. The aqueous phase was extracted twice, each time with 200 ml of ethyl acetate, and the combined organic phases were washed with 200 ml of water, dried (MgSO4), and filtered and concentrated. The residue was dried in a high vacuum. 14.07 g of 2-butyl-5-chloroimidazole-4-carbaldehyde (HPLC content 79.9 percent) was obtained. This corresponds to a yield of 56 percent, based on the methyl pentanimidate. The temperature dropped to -10° C rose again to 0° C the mixture was stirred at room temperature for 3 hours The reaction mixture was stirred for an additional 3 hours methanol and water were removed from the mixture by distillation in vacuo 118.5 g of POCl3 /toluene was distilled off the residue was treated with 121 ml of ethyl acetate and 408 ml of water The pH was adjusted to 1, by addition of 18 ml of 30 percent strength sodium hydroxide solution the phases were separated The aqueous phase was extracted twice each time with 200 ml of ethyl acetate, and the combined organic phases were washed with 200 ml of water dried (MgSO4) filtered concentrated The residue was dried in a high vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5.00 g (39.42 mmol) of glycine methyl ester hydrochloride was added in a single portion to a solution of 1.59 g (39.42 mmol) of sodium hydroxide in 13 ml of methanol, at 0° C. The temperature dropped to -10° C. Then, the mixture was stirred for 15 minutes. During this time, the temperature rose again to 0° C. 4.73 g (39.42 mmol) of methyl pentanimidate was added, and the mixture was stirred at room temperature for 3 hours. 9.00 g (43.36 mmol) of N,N-dimethylformamide dibutyl acetal then was added, during the course of 5 minutes, and the reaction mixture was stirred for a further 3 hours. Then, the solvent was removed on the Rotavapor, and the residue was treated with 40 ml of CH2Cl2 and 15 ml of water. After phase separation, the organic phase was washed with 10 ml of water. The organic phase was dried (MgSO4), filtered and concentrated on the Rotavapor, and the residue was dried in a high vacuum. 6.92 g of 2-butyl-4-dimethylaminomethylene-2-imidazolin-5-one was obtained; the product had a content of about 80 percent according to H-NMR. This corresponds to a yield of about 72 percent, based on the methyl pentanimidate. The temperature dropped to -10° C rose again to 0° C the mixture was stirred at room temperature for 3 hours the reaction mixture was stirred for a further 3 hours Then, the solvent was removed on the Rotavapor the residue was treated with 40 ml of CH2Cl2 and 15 ml of water After phase separation the organic phase was washed with 10 ml of water The organic phase was dried (MgSO4) filtered concentrated on the Rotavapor the residue was dried in a high vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5.00 g (39.42 mmol) of glycine methyl ester hydrochloride was added in a single portion to a solution of 1.59 g (39.42 mmol) of sodium hydroxide in 13 ml of methanol at 0° C. The temperature dropped to -10° C. The mixture was then stirred for 15 minutes and during this time the temperature rose again to 0° C. 4.73 g (39.42 mmol) of methyl pentanimidate was added, and the mixture was stirred at room temperature for 3 hours. Then, during the course of 5 minutes, 5.62 g (43.39 mmol) of N,N-dimethylformamide dimethyl acetal was added, and the reaction mixture was stirred for a further 3 hours. Thereafter, solvent was removed on a Rotavapor, and the residue was treated with 40 ml of CH2Cl2 and 15 ml of water. After phase separation, the organic phase was washed with 10 ml of water, and then the combined H2O phases were washed twice, each time with 20 ml of CH2Cl2. Then, the combined organic phases were dried (MgSO4), filtered, concentrated on the Rotavapor and dried in a high vacuum. 6.70 g of 2-butyl-4-dimethylaminomethylene-2-imidazolin-5-one was obtained, having a content of about 90 percent, according to 1H-NMR. This corresponds to a yield of about 78 percent, based on the methyl pentanimidate. The temperature dropped to -10° C rose again to 0° C the mixture was stirred at room temperature for 3 hours the reaction mixture was stirred for a further 3 hours Thereafter, solvent was removed on a Rotavapor the residue was treated with 40 ml of CH2Cl2 and 15 ml of water After phase separation the organic phase was washed with 10 ml of water the combined H2O phases were washed twice Then, the combined organic phases were dried (MgSO4) filtered concentrated on the Rotavapor dried in a high vacuum

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 31.72 g (250 mmol) of glycine methyl ester hydrochloride was added in a single portion to a solution of 10.13 g (250 mmol) of sodium hydroxide in 80 ml of methanol at 0° C. The temperature dropped to -10° C. The mixture was stirred for 10 minutes, during which time the temperature rose again to 0° C. 108.25 g (a 26.6 percent strength solution in toluene, 250 mmol) of methyl pentanimidate was added, and the mixture was stirred at room temperature for 3 hours. 35.64 g (about 92 percent strength, 275 mmol) of dimethylformamide dimethyl acetal then was added, during the course of 5 minutes. The reaction mixture was stirred for an additional 3 hours. 200 ml of toluene was added, and methanol and water were removed from the mixture by distillation in vacuo. Of the remaining 203.5 g, 91.68 g (corresponding to 112 mmol of methyl pentanimidate) was initially introduced at room temperature and treated with 65.09 g (416 mmol) of POCl3. The mixture was heated 15 100° C. for 1.5 hours and then 118.5 g of POCl3 /toluene was distilled off and the residue was treated with 121 ml of ethyl acetate and 408 ml of water. The pH was adjusted to 1, by addition of 18 ml of 30 percent strength sodium hydroxide solution, and the phases were separated. The aqueous phase was extracted twice, each time with 200 ml of ethyl acetate, and the combined organic phases were washed with 200 ml of water, dried (MgSO4), and filtered and concentrated. The residue was dried in a high vacuum. 14.07 g of 2-butyl-5-chloroimidazole-4-carbaldehyde (HPLC content 79.9 percent) was obtained. This corresponds to a yield of 56 percent, based on the methyl pentanimidate. The temperature dropped to -10° C rose again to 0° C the mixture was stirred at room temperature for 3 hours The reaction mixture was stirred for an additional 3 hours methanol and water were removed from the mixture by distillation in vacuo 118.5 g of POCl3 /toluene was distilled off the residue was treated with 121 ml of ethyl acetate and 408 ml of water The pH was adjusted to 1, by addition of 18 ml of 30 percent strength sodium hydroxide solution the phases were separated The aqueous phase was extracted twice each time with 200 ml of ethyl acetate, and the combined organic phases were washed with 200 ml of water dried (MgSO4) filtered concentrated The residue was dried in a high vacuum

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 31.72 g (250 mmol) of glycine methyl ester hydrochloride was added in a single portion to a solution of 10.13 g (250 mmol) of sodium hydroxide in 80 ml of methanol at 0° C. The temperature dropped to -10° C. The mixture was stirred for 10 minutes, during which time the temperature rose again to 0° C. 108.25 g (a 26.6 percent strength solution in toluene, 250 mmol) of methyl pentanimidate was added, and the mixture was stirred at room temperature for 3 hours. 35.64 g (about 92 percent strength, 275 mmol) of dimethylformamide dimethyl acetal then was added, during the course of 5 minutes. The reaction mixture was stirred for an additional 3 hours. 200 ml of toluene was added, and methanol and water were removed from the mixture by distillation in vacuo. Of the remaining 203.5 g, 91.68 g (corresponding to 112 mmol of methyl pentanimidate) was initially introduced at room temperature and treated with 65.09 g (416 mmol) of POCl3. The mixture was heated 15 100° C. for 1.5 hours and then 118.5 g of POCl3 /toluene was distilled off and the residue was treated with 121 ml of ethyl acetate and 408 ml of water. The pH was adjusted to 1, by addition of 18 ml of 30 percent strength sodium hydroxide solution, and the phases were separated. The aqueous phase was extracted twice, each time with 200 ml of ethyl acetate, and the combined organic phases were washed with 200 ml of water, dried (MgSO4), and filtered and concentrated. The residue was dried in a high vacuum. 14.07 g of 2-butyl-5-chloroimidazole-4-carbaldehyde (HPLC content 79.9 percent) was obtained. This corresponds to a yield of 56 percent, based on the methyl pentanimidate. The temperature dropped to -10° C rose again to 0° C the mixture was stirred at room temperature for 3 hours The reaction mixture was stirred for an additional 3 hours methanol and water were removed from the mixture by distillation in vacuo 118.5 g of POCl3 /toluene was distilled off the residue was treated with 121 ml of ethyl acetate and 408 ml of water The pH was adjusted to 1, by addition of 18 ml of 30 percent strength sodium hydroxide solution the phases were separated The aqueous phase was extracted twice each time with 200 ml of ethyl acetate, and the combined organic phases were washed with 200 ml of water dried (MgSO4) filtered concentrated The residue was dried in a high vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5.00 g (39.42 mmol) of glycine methyl ester hydrochloride was added in a single portion to a solution of 1.59 g (39.42 mmol) of sodium hydroxide in 13 ml of methanol, at 0° C. The temperature dropped to -10° C. Then, the mixture was stirred for 15 minutes. During this time, the temperature rose again to 0° C. 4.73 g (39.42 mmol) of methyl pentanimidate was added, and the mixture was stirred at room temperature for 3 hours. 9.00 g (43.36 mmol) of N,N-dimethylformamide dibutyl acetal then was added, during the course of 5 minutes, and the reaction mixture was stirred for a further 3 hours. Then, the solvent was removed on the Rotavapor, and the residue was treated with 40 ml of CH2Cl2 and 15 ml of water. After phase separation, the organic phase was washed with 10 ml of water. The organic phase was dried (MgSO4), filtered and concentrated on the Rotavapor, and the residue was dried in a high vacuum. 6.92 g of 2-butyl-4-dimethylaminomethylene-2-imidazolin-5-one was obtained; the product had a content of about 80 percent according to H-NMR. This corresponds to a yield of about 72 percent, based on the methyl pentanimidate. The temperature dropped to -10° C rose again to 0° C the mixture was stirred at room temperature for 3 hours the reaction mixture was stirred for a further 3 hours Then, the solvent was removed on the Rotavapor the residue was treated with 40 ml of CH2Cl2 and 15 ml of water After phase separation the organic phase was washed with 10 ml of water The organic phase was dried (MgSO4) filtered concentrated on the Rotavapor the residue was dried in a high vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5.00 g (39.42 mmol) of glycine methyl ester hydrochloride was added in a single portion to a solution of 1.59 g (39.42 mmol) of sodium hydroxide in 13 ml of methanol at 0° C. The temperature dropped to -10° C. The mixture was then stirred for 15 minutes and during this time the temperature rose again to 0° C. 4.73 g (39.42 mmol) of methyl pentanimidate was added, and the mixture was stirred at room temperature for 3 hours. Then, during the course of 5 minutes, 5.62 g (43.39 mmol) of N,N-dimethylformamide dimethyl acetal was added, and the reaction mixture was stirred for a further 3 hours. Thereafter, solvent was removed on a Rotavapor, and the residue was treated with 40 ml of CH2Cl2 and 15 ml of water. After phase separation, the organic phase was washed with 10 ml of water, and then the combined H2O phases were washed twice, each time with 20 ml of CH2Cl2. Then, the combined organic phases were dried (MgSO4), filtered, concentrated on the Rotavapor and dried in a high vacuum. 6.70 g of 2-butyl-4-dimethylaminomethylene-2-imidazolin-5-one was obtained, having a content of about 90 percent, according to 1H-NMR. This corresponds to a yield of about 78 percent, based on the methyl pentanimidate. The temperature dropped to -10° C rose again to 0° C the mixture was stirred at room temperature for 3 hours the reaction mixture was stirred for a further 3 hours Thereafter, solvent was removed on a Rotavapor the residue was treated with 40 ml of CH2Cl2 and 15 ml of water After phase separation the organic phase was washed with 10 ml of water the combined H2O phases were washed twice Then, the combined organic phases were dried (MgSO4) filtered concentrated on the Rotavapor dried in a high vacuum

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A white suspension of 37.91 g (0.50 mol) of glycine, 9.0 g (0.50 mol) of water and 160 ml of methanol was cooled to 0° C. The pH was adjusted to 9.5 by addition of 30 percent strength sodium hydroxide solution. 140.46 g of a solution of methyl pentanimidate (41 percent strength=0.50 mol) in toluene was added dropwise in the course of 11 minutes, so that the temperature could be kept at 0° C. The reaction mixture was stirred for 20 hours at room temperature, after which the pH was adjusted from 10.13 to 7.0 by the addition of concentrated sulfuric acid. 500 ml of toluene was added and methanol and water were distilled off under vacuum. After the distillation, 72.6 g of toluene was added. The weakly yellowish suspension was cooled to 0° C. and 219.0 g (1.40 mol) of phosphorus oxychloride was added in the course of 11 minutes. After 20 minutes, the mixture was heated to 80° C., 102.9 g (1.40 mol) of dimethylformamide was added, the mixture was heated for 2 hours at 100° C., allowed to cool to 35° C. and, with stirring, poured into 350 ml of water so that the temperature could be kept below 30° C. The mixture was admixed with 300 ml of ethyl acetate and 20 g of Celite, and stirred for 15 minutes at 25° to 30° C. The pH was adjusted to 1.20 by the addition of 2.75 ml of 30 percent strength sodium hydroxide solution. The Celite was filtered off with suction at approximately 30° C. and the phases were separated at approximately 30° C. The organic phase was washed twice with water and concentrated to dryness. The yield of the title compound was 68.1 g (HPLC purity 85.0 percent), 62 percent based on glycine. could be kept at 0° C methanol and water were distilled off under vacuum After the distillation, 72.6 g of toluene was added The weakly yellowish suspension was cooled to 0° C. After 20 minutes the mixture was heated to 80° C. the mixture was heated for 2 hours at 100° C. to cool to 35° C. with stirring could be kept below 30° C stirred for 15 minutes at 25° to 30° C The Celite was filtered off with suction at approximately 30° C. the phases were separated at approximately 30° C The organic phase was washed twice with water concentrated to dryness