Structure of 1206102-06-8
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CAS No. : | 1206102-06-8 |
Formula : | C16H17NO6 |
M.W : | 319.31 |
SMILES Code : | O=C(C1=C(OCC2=CC=CC=C2)C(C=CN1CC(O)CO)=O)O |
MDL No. : | MFCD22741606 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one; water at 28 - 33℃; for 15 - 17 h; | A reactor was charged with 1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1 ,4- dihydro-2-pyridinecarboxylic acid 6 (4.302 kg, 13.47 mol) followed by charging withNaHCO3 (1.69 kg, 20.09 mol) and 242 g of deionized water. To this was added 21.4 kg of NMP and the mixture was stirred and temperature brought to 28-35 0C. Dimethyl sulfate (2.34 kg, 18.30 mol) was added dropwise via an addition funnel to the reaction mixture over 1-3 hours keeping the temperature at 28-330C. The slurry was agitated at this temperature for 14 h. When deemed complete, the reaction mixture was cooled to 5 0C or below and the mixture was neutralized to pH 6 by the addition of HCI (561 ml_ of cone HCI in 2806 g of deionized water). The reaction vessel was slowly charged with cold 20percent brine solution composed of 8.7 kg NaCI, 20 kg of deionized water and 14.8 kg of ice at a maximum temperature of 100C. The mixture was agitated at 0-100C for 2.5 h. The slurry was filtered under vacuum and the cake washed with 15 kg of deionized water two times. The wet solid product was dried at 45-55 0C under vacuum until constant weight was obtained. The desired product methyl 1-(2,3-dihydroxypropyl)-4-oxo-3- [(phenylmethyl)oxy]-1 ,4-dihydro-2-pyridinecarboxylate 7 was obtained as a light yellow solid (3.77 kg, 99.42percent purity by HPLC, 84percent). 1H NMR(300 MHz, DMSO-d6) δ 7.60 (d, J = 7.5 Hz, 1 H), 7.36 (m, 5 H), 6.28 (d, J = 7.5 Hz, 1 H), 5.23 (d, J = 5.4 Hz, 1 H), 5.10 (Abq, J = 10.8 Hz, 2 H), 4.85 (m, 1 H), 3.98 (dd, J = 14.3, 2.4 Hz, 1 H), 3.79 (s, 3 H), 3.70 (dd, J = 14.3, 9.0 Hz, 1 H), 3.58 (m, 1 H), 3.23 (m, 1 H). |
84% | With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one; water at 28 - 35℃; Large scale | Areactor was charged with 1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylic acid 6 (4.302 kg, 13.47 mol) followed by charging with NaHCO3(1.69 kg, 20.09 mol) and 242 g of deionized water. To this was added 21.4 kg of NMP and the mixture was stirred and temperature brought to 28-35° C. Dimethyl sulfate (2.34 kg, 18.30 mol) was added dropwise via an addition funnel to the reaction mixture over 1-3 hours keeping the temperature at 28-33° C. The slurry was agitated at this temperature for 14 h. When deemed complete, the reaction mixture was cooled to 5° C. or below and the mixture was neutralized to pH 6 by the addition of HCl (561 mL of conc HCl in 2806 g of deionized water). The reaction vessel was slowly charged with cold 20percent brine solution composed of 8.7 kg NaCl, 20 kg of deionized water and 14.8 kg of ice atamaximum temperature of 10° C. The mixture was agitated at 0-10° C. for 2.5 h. The slurry was filtered under vacuum and the cake washed with 15 kg of deionized water two times. The wet solid product was dried at 45-55° C. under vacuum until constant weight was obtained. The desired product methyl 1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylate 7 was obtained asalight yellow solid (3.77 kg, 99.42percent purity by HPLC, 84percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one at 20℃; for 5 h; | (4) 10 g of Intermediate 4, 7.9 g of sodium hydrogencarbonate and 6.7 g of methyl iodide were added to 20 mL of N-methylpyrrolidone, and the mixture was stirred at room temperature for 5 hours, and the reaction was completed.Under ice water bath, dilute hydrochloric acid adjusts the system pH=4, adding a lot of water,a yellow solid precipitates,Filtered, washed, dried,Yield 9.9 g of a white solid, intermediate 5, yield: 95percent. |
89% | With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one; water at 20℃; for 4 h; | To a slurry of 576 g of compound 6(1.0 eq.: 5.8percent of H2O was contained) in 2.88 L of NMP were added 431 g of NaHCO3(3.0 eq.) and 160 mL of methyl iodide(1.5 eq.) and the mixture was stirred at room temperature for 4 h. After cooling to 5 0C, 1.71 L of 2N HCI and 1.15 L of 20percent NaClaq were added to the mixture at less than 10 0C to give crystal of compound 7. Filtration, washing with 1.73 L of H2O and drying provided 507 g of compound 7 (89percent yield) as a crystal.1H NMR(300 MHz, DMSO-d6) δ 7.59 (d, J = 7.5 Hz, 1 H), 7.40-7.28 (m, 5H), 6.28 (d, J = 7.5 Hz, 1 H)1 5.21 (d, J = 5.4 Hz, 1 H), 5.12 (d, J = 10.8 Hz, 1 H), 5.07 (d, J = 10.8 Hz, 1H), 4.83 (t, J = 5.7 Hz, 1H), 3.97 (dd, J = 2.4, 14.1 Hz, 1 H), 3.79 (s, 3H), 3.70 (dd, J = 9.0, 14.4 Hz, 1 H), 3.65-3.50 (m, 1 H), 3.40-3.28 (m, 1H), 3.26-3.14 (m, 1 H). |
89% | With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one; water at 20℃; for 4 h; | f) Synthesis of methyl 1 -(2,3-dihydroxypropyl)-4-oxo-3- [(phenylmethyl)oxy]-1 ,4-dihydro-2-pyridinecarboxy- late (compound P-7). To a slurry of 576 g of compound P-6 (1.0 eq.: 5.8percent of H20 was contained) in 2.88 E ofNMP were added 431 g of NaHCO3 (3.0 eq.) and 160 mE of methyl iodide (1.5 eq.) and the mixture was stirred at room temperature for 4 h. Afier cooling to 5° C. 1.71 E of 2N HC1 and 1.15 E of 20percent NaClaq were added to the mixture at less than 10° C. to give crystal of compound 7. Filtration, washing with 1.73 E of H20 and drying provided 507 g of compound P-7 (89percent yield) as a solid. ‘H NMR (300 MHz, DMSO-d5) ö 7.59 (d, J=7.5 Hz, 1H), 7.40-7.28 (m, 5H), 6.28 (d, J=7.5 Hz, 1H), 5.21 (d, J=5.4 Hz, 1H), 5.12 (d, J=10.8 Hz, 1H), 5.07 (d, J=10.8 Hz, 1H), 4.83 (t, J=5.7 Hz, 1H), 3.97 (dd, J=2.4, 14.1 Hz, 1H), 3.79 (s, 3H), 3.70 (dd, J=9.0, 14.4 Hz, 1H),3.65-3.50 (m, 1H), 3.40-3.28 (m, 1H), 3.26-3.14 (m, 1H). |
89% | With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one; water at 20℃; for 4 h; | To a slurry of 576 g of compound 6(1.0 eq.: 5.8percent of H2O was contained) in 2.88 L of NMP were added 431 g of NaHCO3(3.0 eq.) and 160 mL of methyl iodide (1.5 eq.) and the mixture was stirred at room temperature for 4 h. After cooling to 5° C., 1.71 L of 2N HCl and 1.15 L of 20percent NaClaq were added to the mixture at less than 10° C. to give crystal of compound 7. Filtration, washing with 1.73 L of H2O and drying provided 507 g of compound 7 (89percent yield) as a crystal. |
55% | With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one at 20℃; Inert atmosphere | Step E - Synthesis of Intermediate Compound A Into a 2-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen. This was followed by the addition of 3-(benzyloxy)-l-(2,3- dihydroxypropyl)-4-oxo-l,4-dihydropyridine-2-carboxylic acid If (200 g, 626.35 mmol, 1.00 equiv), NMP (1000 mL), sodium bicarbonate (158 g, 1.88 mol, 3.00 equiv), CH3I (133.5 g, 940.54 mmol, 1.50 equiv). The resulting solution was stirred overnight at room temperature. The reaction mixture was cooled to 0 °C with a water/ice bath. The resulting solution was diluted with a solution of NaCl (73 g) in 500 mL of H20. Then the pH value of the solution was adjusted to 4 with hydrogen chloride (cone). The reaction mixture was then stirred for another 2 hours. The solids were collected by filtration, washed with water (2x100 mL) and then dried in an oven in vacuo. This resulted in methyl 3-(benzyloxy)-l-(2,3-dihydroxypropyl)-4-oxo-l,4- dihydropyridine-2-carboxylate (117.6 g, 55percent yield) A as a white solid. |
Tags: 1206102-06-8 synthesis path| 1206102-06-8 SDS| 1206102-06-8 COA| 1206102-06-8 purity| 1206102-06-8 application| 1206102-06-8 NMR| 1206102-06-8 COA| 1206102-06-8 structure
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