sodium;2-(methylamino)acetate

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 674.5 g (2.43 moles) of 40% by weight aqueous sodium sarcosinate solution were taken and a pH value of 8.5 adjusted at 70° C. with 99% by weight acetic acid. After the addition of 500 ml methanol, 491.1 g (2.92 moles) of a 25% by weight aqueous cyanamide solution were added thereto with vigorous stirring at reflux temperature in the course of 2 hours. After ending of the addition of the cyanamide solution, the reaction mixture was further stirred for 2 hours under reflux while stirring. After cooling to 15° C., the crystalline precipitate was filtered off with suction, washed twice with, in each case, 250 ml of water and subsequently recrystallised from water. After drying in a vacuum drying cabinet at 80° C. and 15 mbar pressure, there were obtained 176.7 g (48.8% by weight) of anhydrous creatine. were added at reflux temperature in the course of 2 hours the reaction mixture was further stirred for 2 hours under reflux while stirring the crystalline precipitate was filtered off with suction washed twice with, in each case, 250 ml of water subsequently recrystallised from water After drying in a vacuum drying cabinet at 80° C.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 462.5 g (1.67 moles) of a technical 40% by weight aqueous sodium sarcosinate solution and 200 g of water were take. A pH value of 9.81 (at 20° C.) was adjusted with concentrated 98% by weight formic acid. The reaction mixture was heated to 50° C. 138.2 g (1.65 moles) of SKW cyanamide L 500 (technical aqueous cyanamide solution with a content of 50.2% by weight) were added uniformly with vigorous stirring at an internal temperature of 50° to 52° C. over the course of 3 hours. The reaction mixture was further stirred for 1 hour at an internal temperature of 50° C. Subsequently, the reaction product was filtered off with suction and, without washing, suspended in 330 g of water. The suspension was stirred for 2 hours at 20° C. It was then filtered off with suction and the residue washed twice with 100 ml of water. After drying in a vacuum at 30° C. and 20 mbar pressure, there were obtained 165.2 g (67.1% of theory) creatine monohydrate. A pH value of 9.81 (at 20° C.) with concentrated 98% by weight formic acid The reaction mixture was further stirred for 1 hour at an internal temperature of 50° C Subsequently, the reaction product was filtered off with suction without washing The suspension was stirred for 2 hours at 20° C It was then filtered off with suction the residue washed twice with 100 ml of water After drying in a vacuum at 30° C.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 462.5 g (1.67 moles) of a technical 40% by weight aqueous sodium sarcosinate solution and 200 g of water were take. A pH value of 9.81 (at 20° C.) was adjusted with concentrated 98% by weight formic acid. The reaction mixture was heated to 50° C. 138.2 g (1.65 moles) of SKW cyanamide L 500 (technical aqueous cyanamide solution with a content of 50.2% by weight) were added uniformly with vigorous stirring at an internal temperature of 50° to 52° C. over the course of 3 hours. The reaction mixture was further stirred for 1 hour at an internal temperature of 50° C. Subsequently, the reaction product was filtered off with suction and, without washing, suspended in 330 g of water. The suspension was stirred for 2 hours at 20° C. It was then filtered off with suction and the residue washed twice with 100 ml of water. After drying in a vacuum at 30° C. and 20 mbar pressure, there were obtained 165.2 g (67.1% of theory) creatine monohydrate. A pH value of 9.81 (at 20° C.) with concentrated 98% by weight formic acid The reaction mixture was further stirred for 1 hour at an internal temperature of 50° C Subsequently, the reaction product was filtered off with suction without washing The suspension was stirred for 2 hours at 20° C It was then filtered off with suction the residue washed twice with 100 ml of water After drying in a vacuum at 30° C.

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 277.7 g (1 mole) of a technical 40% by weight aqueous sodium sarcosinate solution were used. A pH value of 9.6 (at 20° C.) was adjusted with concentrated hydrochloric acid and heated to 95° C. Subsequently, 105.1 g (1.25 mole) of a technical 50% by weight aqueous cyanamide solution were added thereto with intensive stirring in such a manner that the internal temperature did not exceed 95° C. After ending of the cyanamide addition, further heating was carried out for 1 hour at 95° C. The reaction mixture was then cooled to 15° C. the crystalline precipitate was filtered off with suction and washed chloride-free by washing twice with, in each case, 120 ml of water. The residue was recrystallized from water and dried at 80° C. and 20 mbar. The yield of creatine was 73.4 g (56% of theory). The content determination by means of HPLC gave a content of 100% (creatine monohydrate obtainable pure in chemical commerce was used as standard). A pH value of 9.6 (at 20° C.) did not exceed 95° C further heating The reaction mixture was then cooled to 15° C. the crystalline precipitate was filtered off with suction washed chloride-free by washing twice with, in each case, 120 ml of water The residue was recrystallized from water dried at 80° C.

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

Procedure: JP 077364 describes the reaction of a solution of sodium sarcosinate with O-methylisourea methyl sulfate at pH 11 to give creatine.

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

Procedure: To a 22% (w/w) unprocessed aqueous solution of 6160 g (about 12.2 mol) sodium N-methylglycinate, 20% sulfuric acid was added under stirring and cooling in an ice-salt liquor bath to adjusting the pH to 9.8. The temperature was kept below 15° C. in this process. Under the condition that the internal temperature was kept at 40° C., 3052 g (11 mol) of S-methylisothiourea sulfate was slowly added into the solution under stirring within 100 minutes. Then the solution was further stirred for 15 minutes at an internal temperature not more than 40° C. Thereafter, a hot vapor was fed into the solution for 45 minutes, and a crystal was precipitated. After staying for 7 hours, the solution was centrifuged to remove the mother liquor, then was washed with distilled water several times (80 ml each time) until pH value becomes to ≦7.6. The product was washed once with 1100 ml of 95% ethanol to obtain a crude product. 1260 ml of water was added to the crude product, and the mixture was heated to 45° C. under stirring. Then pH was adjusted to 7.0 with addition of 10% sulfuric acid. Thereafter, the temperature was raised to 80° C. Then 0.5 g of disodium EDTA was added thereto, and the temperature was raised to 90° C. After stirring for 15 minutes, the solution was filtered. The filtrate was cooled to a temperature below 20° C., and a crystal was obtained. The crystalline product was recovered by centrifugation, washed once with 50 ml of distilled water and once with 70 ml of 95% ethanol, and dried in a vacuum drier at 40° C. under 20 millibar pressure. 1044 g of the product (S-methylisothiourea was used as the standard) was obtained. The yield of creatine-monohydrate was 70.3, and the content or purity (HPLC) was 99.4%. After dehydrated at 80° C., creatine was obtained. There was substantially no product loss in this process. cooling in an ice-salt liquor bath was kept below 15° C. in this process was kept at 40° C. under stirring within 100 minutes Then the solution was further stirred for 15 minutes at an internal temperature not more than 40° C a crystal was precipitated After staying for 7 hours to remove the mother liquor was washed with distilled water several times (80 ml each time) until pH value The product was washed once with 1100 ml of 95% ethanol to obtain a crude product under stirring Thereafter, the temperature was raised to 80° C the temperature was raised to 90° C After stirring for 15 minutes the solution was filtered The filtrate was cooled to a temperature below 20° C. a crystal was obtained The crystalline product was recovered by centrifugation washed once with 50 ml of distilled water and once with 70 ml of 95% ethanol dried in a vacuum drier at 40° C. under 20 millibar pressure was obtained After dehydrated at 80° C.

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

Procedure: To a 22% (w/w) unprocessed aqueous solution of 6160 g (about 12.2 mol) sodium N-methylglycinate, 20% sulfuric acid was added under stirring and cooling in an ice-salt liquor bath to adjusting the pH to 9.8. The temperature was kept below 15° C. in this process. Under the condition that the internal temperature was kept at 40° C., 3052 g (11 mol) of S-methylisothiourea sulfate was slowly added into the solution under stirring within 100 minutes. Then the solution was further stirred for 15 minutes at an internal temperature not more than 40° C. Thereafter, a hot vapor was fed into the solution for 45 minutes, and a crystal was precipitated. After staying for 7 hours, the solution was centrifuged to remove the mother liquor, then was washed with distilled water several times (80 ml each time) until pH value becomes to ≦7.6. The product was washed once with 1100 ml of 95% ethanol to obtain a crude product. 1260 ml of water was added to the crude product, and the mixture was heated to 45° C. under stirring. Then pH was adjusted to 7.0 with addition of 10% sulfuric acid. Thereafter, the temperature was raised to 80° C. Then 0.5 g of disodium EDTA was added thereto, and the temperature was raised to 90° C. After stirring for 15 minutes, the solution was filtered. The filtrate was cooled to a temperature below 20° C., and a crystal was obtained. The crystalline product was recovered by centrifugation, washed once with 50 ml of distilled water and once with 70 ml of 95% ethanol, and dried in a vacuum drier at 40° C. under 20 millibar pressure. 1044 g of the product (S-methylisothiourea was used as the standard) was obtained. The yield of creatine-monohydrate was 70.3, and the content or purity (HPLC) was 99.4%. After dehydrated at 80° C., creatine was obtained. There was substantially no product loss in this process. cooling in an ice-salt liquor bath was kept below 15° C. in this process was kept at 40° C. under stirring within 100 minutes Then the solution was further stirred for 15 minutes at an internal temperature not more than 40° C a crystal was precipitated After staying for 7 hours to remove the mother liquor was washed with distilled water several times (80 ml each time) until pH value The product was washed once with 1100 ml of 95% ethanol to obtain a crude product under stirring Thereafter, the temperature was raised to 80° C the temperature was raised to 90° C After stirring for 15 minutes the solution was filtered The filtrate was cooled to a temperature below 20° C. a crystal was obtained The crystalline product was recovered by centrifugation washed once with 50 ml of distilled water and once with 70 ml of 95% ethanol dried in a vacuum drier at 40° C. under 20 millibar pressure was obtained After dehydrated at 80° C.

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1315 g of a 40% strength aqueous sodium sarcosinate solution (pH 14) were introduced into a 2 1 three-necked flask having a mechanical stirrer, heating bath, reflux condenser and gas inlet tube and the mixture was adjusted to pH 9 by introduction of carbon dioxide gas. After heating the solution to 75° C., 338 g of a 50% strength aqueous cyanamide solution were added in the course of 4 hours. The temperature was kept constant at 75° C. during the entire addition period. The pH remained between 9 and 10 without introduction of further CO2 gas. After the addition of cyanamide, the reaction solution was stirred for 2 hours and then cooled to 35° C. The precipitated creatine was filtered off, washed with water and dried. 480 g of creatine monohydrate having a crystal yield of 75% were obtained. heating bath reflux condenser and gas inlet tube The temperature was kept constant at 75° C. during the entire addition period cooled to 35° C The precipitated creatine was filtered off washed with water dried

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

Procedure: JP 077364 describes the reaction of a solution of sodium sarcosinate with O-methylisourea methyl sulfate at pH 11 to give creatine.

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4625 g (16.7 mol) of a 40% by weight sodium sarcosinate solution prepared according to example 1 was added first. A pH of 9.6 (at 20° C.) was adjusted using concentrated hydrochloric acid while cooling externally with cold water and stirring vigorously. Subsequently it was heated to 75° C. 1403 g (16.7 mol) of a 50% by weight aqueous cyanamide solution (Degussa-Cyanamide L 500) was added uniformly over a period of 90 minutes while stirring vigorously at an internal temperature of 75 to 80° C. After the cyanamide addition was completed, the reaction mixture was stirred for a further 2 hours at an internal temperature of 75° C. After cooling to 5° C., the crystalline reaction product that can be readily filtered was suction filtered, washed three times chloride-free with 1250 ml water in each case and dried in a vacuum-drying cabinet at 40° C. and 20 mbar. The yield was 1897 g creatine monohydrate (corresponds to a yield of 76.2% of theory). was added first A pH of 9.6 (at 20° C.) while stirring vigorously at an internal temperature of 75 to 80° C the reaction mixture was stirred for a further 2 hours at an internal temperature of 75° C After cooling to 5° C. the crystalline reaction product that can be readily filtered filtered washed three times chloride-free with 1250 ml water in each case dried in a vacuum-drying cabinet at 40° C.

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 674.5 g (2.43 moles) of 40% by weight aqueous sodium sarcosinate solution were taken and a pH value of 8.5 adjusted at 70° C. with 99% by weight acetic acid. After the addition of 500 ml methanol, 491.1 g (2.92 moles) of a 25% by weight aqueous cyanamide solution were added thereto with vigorous stirring at reflux temperature in the course of 2 hours. After ending of the addition of the cyanamide solution, the reaction mixture was further stirred for 2 hours under reflux while stirring. After cooling to 15° C., the crystalline precipitate was filtered off with suction, washed twice with, in each case, 250 ml of water and subsequently recrystallised from water. After drying in a vacuum drying cabinet at 80° C. and 15 mbar pressure, there were obtained 176.7 g (48.8% by weight) of anhydrous creatine. were added at reflux temperature in the course of 2 hours the reaction mixture was further stirred for 2 hours under reflux while stirring the crystalline precipitate was filtered off with suction washed twice with, in each case, 250 ml of water subsequently recrystallised from water After drying in a vacuum drying cabinet at 80° C.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 462.5 g (1.67 moles) of a technical 40% by weight aqueous sodium sarcosinate solution and 200 g of water were take. A pH value of 9.81 (at 20° C.) was adjusted with concentrated 98% by weight formic acid. The reaction mixture was heated to 50° C. 138.2 g (1.65 moles) of SKW cyanamide L 500 (technical aqueous cyanamide solution with a content of 50.2% by weight) were added uniformly with vigorous stirring at an internal temperature of 50° to 52° C. over the course of 3 hours. The reaction mixture was further stirred for 1 hour at an internal temperature of 50° C. Subsequently, the reaction product was filtered off with suction and, without washing, suspended in 330 g of water. The suspension was stirred for 2 hours at 20° C. It was then filtered off with suction and the residue washed twice with 100 ml of water. After drying in a vacuum at 30° C. and 20 mbar pressure, there were obtained 165.2 g (67.1% of theory) creatine monohydrate. A pH value of 9.81 (at 20° C.) with concentrated 98% by weight formic acid The reaction mixture was further stirred for 1 hour at an internal temperature of 50° C Subsequently, the reaction product was filtered off with suction without washing The suspension was stirred for 2 hours at 20° C It was then filtered off with suction the residue washed twice with 100 ml of water After drying in a vacuum at 30° C.