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Chemical Structure| 154467-16-0

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Product Details of [ 154467-16-0 ]

CAS No. :154467-16-0
Formula : C9H17N3O6
M.W : 263.25
SMILES Code : O=C(N1CCOCC1)NCCN.O=C(O)C(O)=O
MDL No. :MFCD11113112
InChI Key :FMVSRINQKOORMK-UHFFFAOYSA-N
Pubchem ID :46856355

Safety of [ 154467-16-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 154467-16-0 ]

* 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.

  • Downstream synthetic route of [ 154467-16-0 ]

[ 154467-16-0 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 1398109-46-0 ]
  • [ 154467-16-0 ]
  • [ 133242-30-5 ]
YieldReaction ConditionsOperation in experiment
70.7% Example 5 Landiolol (1) A solution of (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 3-(4-((2R)-3-chloro-2-hydroxypropoxy)phenyl)propanoate (5) prepared according to Example 3 (0.30 g, 0.805 mmol) in acetonitrile (6.0 ml) is added with potassium carbonate 0.45 g (3.22 mmol), and KI 0.013 g (0.0805 mmol), then refluxed for 2 h and added with 2-(morpholine-4-carboxamido)ethanamino oxalate (6) (0.64 g, 2.42 mmol). The mixture is refluxed under stirring, monitoring by UPLC. After completion of the reaction, ethyl acetate (10 ml) and water (10 ml) are added and the phases are separated. The organic phase is added with water (10 ml) and adjusted to pH 4-5 with hydrochloric acid, the phases are separated and the resulting aqueous phase is then adjusted to pH 11-12 with sodium hydroxide and re-extracted with ethyl acetate (10 ml). Then the solvent is evaporated off under reduced pressure to obtain 0.29 g (70.7%) of a pale yellow oil which solidifies in time to a pale yellow solid. LC-MS (ESI+) [M+H]+ = 510 1H-NMR (CDCl3) (chemical shifts expressed in ppm with respect to TMS) (assigned based on the hetero correlation HSQC spectrum): 1.36 (3H, s, CH3); 1.42 (3H, s, CH3); 2.63 (2H, t, J = 7 Hz, CH2-Ar); 2.75 - 2.93 (8H, m, CH2-CO, CH-CH2-NH, CH2-CH2-NH, NH and OH); 3.35 (6H, m, 2CH2-N morpholine and CH2-NH); 3.65 (4H, m, 2CH2-O morpholine), 3.68 (1H, m, CH in 4 oxolane); 3.94 (2H, bd, CH2-OAr); 4.00 - 4.20 (4H, m, CH in 4 oxolane, CH2-OCO and CH in 5 oxolane); 4.25 (1H, m, CH-OH); 5.21 (1H, bt, NH carbamate); 6.83 and 7.11 (4H, system AA'XX', aromatics). 13C-NMR (CDCl3) (ppm) (multiplicity was assigned by DEPT-135): 25.3 (CH3); 26.6 (CH3); 29.9 (CH2); 35.8 (CH2); 40.2 (CH2); 43.8 (CH2-N morpholine); 49.2 (CH2); 51.5 (CH2); 64.6 (CH2); 66.2 (CH2); 66.4 (CH2-O morpholine); 68.3 (CH); 70.3 (CH2); 73.4 (CH); 109.7; 114.4 (CH); 129.2 (CH); 132.8; 157.0; 158.0; 172.5 (COOR). FT-IR (UATR, cm-1): 3350. 2858, 1735, 1626, 1512, 1454, 1371, 1244, 1153, 1115, 1040. 829, 733.
70.7% With sodium hydride; potassium carbonate; potassium iodide; In acetonitrile; for 2h;Reflux; (S) -2,2-dimethyl-1,3-dioxolan-4-yl) methyl 3- (4 - ((R) -3-chloro- 0.45 g (3.22 mmol) of potassium carbonate and 0.013 g (0.0805 mmol) of potassium iodide were added to a solution (0.30 g, 0.805 mmol) of sodium hydrideThen, reflux and add 2- (morpholine-4-carboxamide) ethane amino oxalate (6) (0.64 g, 2.42 mmol) for two hours.The mixture is refluxed while being stirred while being monitored by UPLC.After the reaction was complete, ethyl acetate (10 ml) and water (10 ml) were added,Phase.Water (10 ml) was added to the organic phase, adjusted to pH 4-5 with hydrochloric acid,The phases are separated and the resulting aqueous phase is then adjusted to pH 11-12 with sodium hydroxide and re-extracted with ethyl acetate (10 ml).The solvent is then evaporated under reduced pressure to give 0.29 g (70.7%) of a pale yellow oil which solidifies in the course of time to a pale yellow solid.
  • 2
  • [ 154467-16-0 ]
  • [ 144256-11-1 ]
  • [ 106-89-8 ]
  • [ 144481-98-1 ]
YieldReaction ConditionsOperation in experiment
49.7% Example 7 Landiolol hydrochloride (2) from (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 3-(4-hydroxyphenyl)propanoate (3) A suspension of (R,R)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-ciclohexanediamino cobalt (16) (47 mg, 0.0780 mmol) in dichloromethane (1 ml) is added with 4-nitrobenzoic acid 17 (27 mg, 0.156 mmol). The mixture is left under stirring for 45' at 20-25C until a dark color appears. The resulting solution is concentrated to a volume of about 0.5 ml, added with 0.5 ml of MTBE, concentrated to a volume of 0.5 ml and finally added with 0.5 ml of MTBE, then with (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 3-(4-hydroxyphenyl)propanoate (3), (0.5 g, 1,77 mmol) and then with epichlorohydrin (compound of formula 4 in which X is chlorine) (0.37 g, 3,89 mmol). The mixture is left under stirring at 20-25C, monitoring by UPLC. After completion of the reaction, toluene (10 ml) and water (10 ml) are added and the phases are separated. The organic phase is evaporated recovering the enriched (S)-epichlorohydrin, then added again with toluene (10 ml) and washed with 10% NaOH (10 ml). The resulting solution is concentrated to a volume of about 2 ml, added with 5 ml of acetonitrile, concentrated to a volume of 2 ml and finally added with 10 ml of acetonitrile). The suspension is filtered thus recovering the catalyst and the solution is added with potassium carbonate 0.79 g (5,64 mmol), and KI 0.026 g (0.161 mmol), refluxed for 2 h, then added with 2-(morpholine-4-carboxamido)ethanamino oxalate (6) (1.07 g, 4.03 mmol). The mixture is refluxed under stirring, monitoring by UPLC. After completion of the reaction, ethyl acetate (20.0 ml) and water (20 ml) are added and the phases are separated. The organic phase is then adjusted to pH 4-5 with hydrochloric acid and extracted with water (20 ml). The phases are separated and the resulting aqueous phase is then adjusted to pH 11-12 with sodium hydroxide and re-extracted with ethyl acetate (20 ml). The resulting solution is concentrated to a volume of about 5 ml, added with 20 ml of isopropanol, concentrated to a volume of 5 ml and finally added with 30 ml of isopropanol, then 18% isopropanol hydrochloric acid (0.24 g, 1.18 mmol). The solvent is then evaporated off under reduced pressure and the residue is crystallized from acetone (10 ml). The suspension is filtered and the crystal is dried at 25C for 12 h to obtain 0.48 g (49.7% total, enantiomeric purity: 99.8%) of a white solid. m.p.: 126C (from literature 123-127C) LC-MS (ESI+) [M+H]+ = 510 FT-IR (UATR, cm-1): 3265, 2941, 2789, 2419, 1723, 1615, 1538, 1515, 1435, 1371, 1260. 1242, 1196, 1118, 1047, 887, 838, 821, 771.
  • 3
  • [ 154467-16-0 ]
  • [ 144-62-7 ]
  • [ 144256-12-2 ]
  • [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl-3-{4-[(2S)-2-hydroxy-3-[(2-[(morpholin-4-yl)carbonyl]amino}ethyl)amino]propoxy]phenyl}propanoate oxalate [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% Preparation Example 1the compounds of embodimentTo the reaction flask was added compound 1565.5g, 3000g of water, stirring until the temperature t = 45 , clear solution, 40% sodium hydroxide with 1190g (475g of sodium hydroxide dissolved in 715g of water) was adjusted pH10 ~ 11, the control temperature is low at 50 , a large yellow solid precipitates, the ice bath was cooled to 30 ~ 35 , compound 500g, N, N- dimethylformamide 3000g, incubated at 30 ~ 35 reaction 3 ~ 4h, TLC confirmed that the reaction compound after completion, filtered and the filtrate was extracted 800mL × 3 isopropyl ether, the aqueous layer was collected, extracted with 3000mL × 4 of ethyl acetate, the combined organic layers were washed with brine 5000mL × 3. The organic layer was collected, dried over anhydrous sodium 2000g, charcoal 100g, dried decolorized by stirring 2 ~ 3h. Filtered and the filtrate evaporated to dryness in the vacuum at 60 , the residue was added ethanol 5.0kg, clear solution after stirring was added anhydrous oxalic acid 120g, stirred solution was warmed to clear, and then stirred at normal temperature crystallization, filtration, and dried under reduced pressure as a white crystalline powder 490g, yield 55.0%, HPLC99.8%, single impurity less than 0.1%.
  • 4
  • [ 144-62-7 ]
  • [ 93605-74-4 ]
  • [ 107-15-3 ]
  • [ 154467-16-0 ]
YieldReaction ConditionsOperation in experiment
89.8% In the reactor, add 230.0kg ethylenediamine,Under stirring, 93.0kg of N-phenoxycarbonylmorpholine was added, the temperature was raised to 64-70C, and the reaction was carried out for 6 hours.Recover ethylenediamine by distillation under reduced pressure, and when there is no liquid dripping,The temperature is controlled at 70±2C, and the vacuum distillation is continued for 1 hour.Reduce to room temperature, add 370.0kg of acetone, add 30% sodium hydroxide solution dropwise with stirring, adjust pH 11~12, precipitate a large amount of solids, filter, and concentrate the filtrate to recover acetone. Add 350.0 kg of water to the residue, stir to dissolve, control the temperature at 20C to 40C, add oxalic acid solids in batches to adjust to pH 2 to 3, and precipitate a small amount of solids. Spin filtration, concentrate the filtrate to a slurry state, add 600 kg of ethanol, reflux for 0.5 hours, and filter pressure to a crystallization tank. Cool down and crystallize, keep at 0~10C for 4 hours, filter, and dry the filter cake in a hot-air circulating oven at 50-60C for 8 hours to obtain almost white N-(2-aminoethyl)-4-morpholinecarboxamide oxalate The solid was 106.1kg, and the yield was 89.8%. HPLC purity: 99.97%, moisture: 0.7%, ethylenediamine: 0.02%, ethanol: 7ppm.
80.23% Room temperature, Ethylenediamine (18.03 g) and 50 mL of dichloromethane were added to a 250 mL three-necked flask, Stir, A solution of 9.1 g of N-imidazole-4-morpholine formamide in dichloromethane (100 mL) was slowly added dropwise under constant pressure, Heating up to reflux, Reaction about 36h; After completion of the reaction, methylene chloride was distilled off at room temperature under reduced pressure, 65 C, Decompression to P ≤-0.07Mpa, The remaining ethylenediamine was distilled off, To no fractions, The remaining system was added to 20 mL of methanol, Continue at 65 C, Decompression to P ≤-0.07Mpa distillation, To no fractions, The remaining system was added to 20 mL of dichloromethane, Followed by distillation at 65 C under reduced pressure, To no fractions; Finally, 50mL of methanol dissolved, Ice bath temperature is less than 10 deg C, Slowly dropping oxalic acid in methanol solution, Until the pH value of 4 to 5 to stop dropping, filter, The filtrate was concentrated to no fractions, Ethyl acetate was added to 80 mL overnight, Precipitation of white solid, filter, Collecting filter cake, Dried in vacuo (35 C) to give 10.56 g of intermediate III, The yield was 80.23%;
  • 5
  • [ 154467-16-0 ]
  • [ 69630-16-6 ]
YieldReaction ConditionsOperation in experiment
99.5% With sodium sulfate; sodium hydroxide; In dichloromethane; at 30℃;Large scale; Add 30 kg of dichloromethane to the reaction kettle and after 3.0 kg of N-(2-aminoethyl)-4-morpholinecarboxamide oxalate, Add 5.0 kg of anhydrous sodium sulfate, Sodium hydroxide 1.14kg. The reaction was carried out at 30 C for 15-18 h. filter, the filtrate was concentrated to dryness under reduced pressure. Get about 1.97kg of light yellow oil, The yield was 99.5%.
84.67% With sodium hydroxide; In water; at 20 - 47℃; for 0.333333h;pH 10-11.5; At room temperature, 15.8 g of the compound represented by the formula III and 47.4 g of water were added to a 100 mL reaction flask, Stir, Heating to 43 ~ 47 deg C full solution, 40% sodium hydroxide solution was added dropwise with stirring, Adjust the pH to 10 ~ 11.5, Keep warm for about 20 minutes; Cooled to room temperature, filter, The filter cake was rinsed with 7.2 g of water, The filtrate into the rotary bottle, At a temperature of 44 to 48 C and a pressure of P ≤ -0.07 MPa, Concentrated to no distillate distillate, The remaining residue was reduced to room temperature, Adding 110 g of acetone, Stirring to the residue all dispersed in acetone ,And then transferred into a 250mL Erlenmeyer flask, 9.48 g of anhydrous sodium sulfate was dried for 3 hours, filter, The filtrate was transferred to an eggplant-shaped flask and concentrated by rotary evaporation until no fraction, To give pure intermediate of formula IV, A light yellow oil, 8.8 g, The yield was 84.67%.
  • 6
  • [ 154467-16-0 ]
  • [ 133242-30-5 ]
  • 7
  • [ 154467-16-0 ]
  • landiolol hydrochloride [ No CAS ]
  • 8
  • [ 154467-16-0 ]
  • [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 3-{4-[(2S)-2-hydroxypropoxy]phenyl}propanoate [ No CAS ]
  • [ 144481-98-1 ]
YieldReaction ConditionsOperation in experiment
78.4% Dissolve 80g of N-(2-aminoethyl)-4-morpholinecarboxamide oxalate obtained in Example 1 above in 350ml of water, adjust pH=9 with 40% sodium hydroxide at 40, and remove sodium oxalate by filtration , Add 56g [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 3-{4-[(2S)-2-hydroxypropoxy]phenyl}propanoate solution in isopropanol. The reaction was stirred at 30C for 8 hours, filtered, and concentrated under reduced pressure to remove isopropanol. Then sodium chloride was added to saturation, extracted with 1L of ethyl acetate, dried over anhydrous sodium sulfate and filtered to obtain the ethyl acetate solution of crude landirol.Add 600 ml of saturated ammonium chloride aqueous solution to the above organic phase, stir for 2 hours, extract, and repeat the operation twice. The organic phase was concentrated to dryness under reduced pressure to obtain a pale yellow solid. Then add it to the reaction flask, add ethyl acetate to dissolve it, add dropwise 14% hydrochloric acid ethyl acetate solution, adjust the pH 4 to 4.5, and precipitate flocs. After heating and dissolving, the solid was naturally cooled down, filtered, the filter cake was washed 3 times with ethyl acetate, and dried in a vacuum drying oven at 35-40C to obtain 71.3g of landirol hydrochloride, with a yield of 78.4% and a purity of 99.7%. The obtained finished product has high yield and good quality, and meets the needs of raw materials.
 

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