1-Ethyl-3-methylimidazolium acetate

1-Ethyl-3-methylimidazolium bromine (0.2 mol) and lead (II) acetate trihydrate (0.1 mol) were dissolved in 30 mL of distilled water and 70 mL of distilled water, respectively. After they were completely dissolved, 1-ethyl-3-methylimidazolium bromine solution was poured into lead (II) acetate trihydrate solution under vigorous mechanical stirring. The reaction was carried out at 35 °C for 48 h under nitrogen atmosphere. Then the reaction system was refrigerated at 3 °C for 12 h and the precipitates were filtered off. The filtrates were distilled under reduced pressure to remove the water. The obtained EMIMAc (moisture content  0.02percent; bromide content  0.004percent) was light yellow viscous liquid and the yield was 93percent.First, 1-ethyl-3-methyl-imidazole acetate ion was preparedliquid, In a 250 ml round bottom three-necked flask, 0.1 mol of 1-ethyl-3-methylimidazolium bromide was added(19.lg) and 2.5mol of potassium acetate (245.3g)160 ml of isopropanol was added to dissolve it, Stir at room temperature for 36 h. filter, Removal of insoluble material, The filtrate was steamed at 70 ° C for 8 h, To give a pale yellow oil, Dissolved in 80 ml of methylene chloride, And adding activated carbon powder at room temperature for 17h, Filtered, washed with carbon tetrachloride 3 times, The combined filtrates were evaporated in vacuo to remove the solvent, Yellow oil was obtained, The product was dried in vacuo at 70 ° C to give the desired product. 1-ethyl-3-methyl-imidazole acetate ion liquidLg, And 10 g of D-glucosamine hydrochloride having a molecular weight of 215. 5 was added, Adding equimolar amounts of boric acid with D-glucosamine hydrochloride, After mixing in 50 ml of dimethylsulfoxide, the reaction was carried out at 25 ° C for 48 hours. After completion of the reaction, At room temperature, 20 ml of the reaction product solution, 20 ml of acetonitrile were added, Extraction three times, Remove insoluble impurities, Concentrated by rotary evaporation, And allowed to stand for 10 hours to obtain deoxyfructose, Extraction agent recovery, Recovery and Reuse of Imidazole Ionic Liquids. The conversion rate of the reaction raw material D-glucosamine hydrochloride was 100percentCrystallization gave the product a purity of 97percent, The molar yield of deoxyfructose 60percentSynthesis of 1-ethyl-3-methylimidazolium acetate ([Emim] Ac) in one step To a 500 ml round bottom flask was added 1.2 mol of bromoethane and 0.5 mol of lead acetate, To the constant-pressure dropping funnel was added 1 mol of N-methylimidazole, The reaction was carried out in an ultrasonic microwave combined reactor, The knob of the constant-pressure dropping funnel was controlled so that 1 mol of N-methylimidazole was dropped in one minute, The left through the cooling water, Set the ultrasonic power to 1000W, Microwave heating power of 900W, The reaction was carried out at 50 ° C for 30 minutes. The content of the target product [Emim] Ac in the reaction mixture was determined to be 92percent by nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry.Acetic acid 44 ml was added to a 250 ml Erlenmeyer flask containing 43 ml Ethanol. 6 ml 1-Methylimidazol was then added slowly to the stirred mixture. The mixture was then sealed inside a parr reactor whit continuous stirring for 72 hours at a temperature of 165 °C. The resulting dark liquid was placed in a rotary evaporator at 50 °C water bath. The mixture was then fed to a vacuum distillation equipment to remove the precursor and excess acetic acid. The still remaining liquid was then finally purified by Flash chromatography in a C18 pre-packet column with water as the eluent . The light yellow fractions were saved. This step was repeated 4 times. The final product was dissolved twice in 99, 5percent ethyl alcohols and subjected to vacuum treatment. Yield 17percent. [Emim] Br (19.107 g, 0.1 mol) was placed in a 100 mL three-necked flask, Dissolve anhydrous sodium acetate (8.2g, 0.15mol) in anhydrous methanol (35mL) at 40 C.Slowly add the methanol solution of anhydrous sodium acetate to the three-necked flask using a constant pressure dropping funnel.After the dropwise addition, place it at 0 C or lower and vacuum filter.The filtrate was rotary evaporated to remove the solvent, and dried under vacuum at 80 C for 24h.The product was obtained as a pale yellow viscous liquid (14.46 g, 85%).1.0 mol of 1-ethyl-3-methylimidazolium chloride was dissolved in 48 g of water.Solution A was obtained, and 1.2 mol of lithium perchlorate was dissolved in 254 g of water.Solution B was obtained; solution A was mixed with solution B, and 575 g of dichloromethane was added.Mechanically stir the reaction for 12 hours; dispense the liquid, separate the aqueous phase into waste liquid, Recycling, the organic phase is washed with 260g of pure water each time, and washed 5 times.No precipitation was detected using AgNO3 solution; the organic phase was vacuum-screwed at 80 C.Obtaining 193 g of 1-ethyl-3-methylimidazolium perchlorate ionic liquid intermediate in a yield of 91.9%; adding 579 g of ethanol with vigorous stirringSlowly added a total of 70.6 g of ammonium acetate in 4 batches, during the addition process, Solid solution and precipitation continued, stirring reaction continued for 24 hours; stirring was stopped.Freeze to -15 C for 24 hours, filter, filter cake recovery, the filtrate is steamed 80 degrees; cooled to room temperature, Add 4 volumes of a mixed solution of dichloromethane and 18-crown-6 (crown ether is mixed with dichloromethane in advance, 1% by mass of methylene chloride, frozen to -15 C for 24 hours, filtered, and the filtrate was steamed at 60 degrees;The 18-crown-6 liquid was removed to obtain a total of 154.0 g of 1-ethyl-3-methylimidazolium acetate ionic liquid, and the yield was 90.5%.The purity was determined by high performance liquid chromatography to be 99.0%, the ammonium residue was '120 ppm, and the Cl ion residue was '5 ppm.1.0 mol of 1-ethyl-3-methylimidazolium chloride was dissolved in 48 g of water.Solution A was obtained, and 1.2 mol of lithium perchlorate was dissolved in 254 g of water.Solution B was obtained; solution A was mixed with solution B, 575 g of dichloromethane was added, and the reaction was mechanically stirred for 12 hours;The aqueous phase is separated into waste liquid, recovered, and the organic phase is washed with 260 g of pure water each time.After washing 5 times, no precipitation was detected using AgNO3 solution; the organic phase was vacuum-screwed at 80 C.193 g of 1-ethyl-3-methylimidazolium perchlorate ionic liquid intermediate were obtained in a yield of 91.9%;Add 579g of ethanol and slowly add a total of 90.1g of potassium acetate in 4 batches with vigorous stirring.During the addition process, solids are dissolved and precipitated continuously, and the reaction is continuously stirred for 24 hours;Stirring was stopped, frozen to -15 C for 24 hours, filtered, and the filter cake was recovered. The filtrate was steamed at 80 C; cooled to room temperature.Add 4 volumes of a mixed solution of dichloromethane and 18-crown-6 (crown ether is mixed with dichloromethane in advance, 1% of the mass of methylene chloride, frozen to -15 C for 24 hours, filtered, the filtrate was steamed at 60 C; 18-crown-6 liquid separation, A total of 154.0 g of 1-ethyl-3-methylimidazolium acetate ionic liquid was obtained, and the yield was 90.5%.The purity was 99.3% by high performance liquid chromatography, '120ppm of K ion residue, and '5ppm of Cl ion residue.1.0 mol of 1-ethyl-3-methylimidazolium chloride was added to 880 g of ethanol with vigorous stirring.Slowly add a total of 90.1 g of potassium acetate in 4 batches, during the addition process, The solids were dissolved and precipitated continuously, and the reaction was stirred for 24 hours; the stirring was stopped, and the mixture was frozen to -15 C for 24 hours.Filtration, recovery of the cake, and evaporation of the filtrate at 80 degrees to obtain a total of 153.0 g of 1-ethyl-3-methylimidazolium acetate ionic liquid, the yield was 90.0%.The purity was determined by high performance liquid chromatography to be 97.0%, the K ion residue was about 8200 ppm, and the Cl ion residue was about 6400 ppm.1.0 g of roxadustat of form A was dosed into a flask and dissolved in 30 ml of THF. Subsequently, during 20 minutes, a solution of 3 -ethyl- 1 -methyl- lH-imidazol-3-ium acetate in dichloromethane (30 ml) was added by dripping and the mixture was stirred for 22 h at the room temperature (25C). After evaporation of approximately a half of the reaction mixture volume, the suspension was filtered and washed with a minimal quantity of THF. The product was obtained in the form of white powder in the yield of 0.59 g (51%) and with 99.8% purity (determined by means of UHPLC). An IR measurement confirmed formation of a salt. Ratio of roxadustate: 3 -ethyl- 1 -methyl- lH-imidazol-3-ium = 2:1, contents of solvents: 0.05 molar equivalents of THF and 0.05 molar equivalents of dichloromethane, determined by means of NMR. (0397) 1H-NMR (500 MHz, DMSO-d6): 9.16 (0.5H, s, AiH), 8.90 (1H, t, J= 4.8 Hz, NH), 8.29 (1H, d, J = 9.2 Hz, ArH), 7.77 (0.5 H, t, J = 1.8 Hz, ArH), 7.69 (0.5 Eta, t, J = 1.8 Hz, AiH), 7.61 (1H, d, J= 2.3 Hz, ArH), 7.52 (1Eta, dd, J= 9.0, 2.4 Hz, ArH), 7.48 (2Eta, -t, J = 7.4 Hz, ArH), 7.25 (1Eta, ~t, J= 7.4 Hz, ArH), 7.18 (2Eta, ~d, J= 8.6 Hz, ArH), 4.18 (1Eta, q, J= 7.2 Hz, CH2), 3.84 (1.5H, s, CH3), 3.81 (2Eta, d, J= 5.2 Hz, CH2), 2.69 (3Eta, s, CH3), 1.40 (1.5Eta, t, CH3). 13C NMR (125 MHz, DMSO-d6): 169.95, 169.06, 157.64, 155.60, 152.75, 146.67, 136.32, 131.30, 130.37, 125.21, 124.50, 123.64, 123.57, 122.40, 121.97, 119.71, 119.46, 112.18, 44.10, 42.13, 35.68, 21.53, 15.11. (0398) A TGA measurement confirmed the presence of 2, 2% of water. (0399) The X-ray powder pattern of 3 -ethyl- 1 -methyl- lH-imidazol-3-ium roxadustat is shown in Fig. 62, the DSC record is shown in Fig. 63; this is a crystalline form with the melting point of 160C.As in Example 37 except that 3.4 g of triphenylsulfonium bromide (manufactured by Tokyo Chemical Industry Co., Ltd.) was changed to 1.7 g (10 mmol) of

Molecular Weight:170.21
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:170.105527694
Monoisotopic Mass:170.105527694
Topological Polar Surface Area:48.9
Heavy Atom Count:12
Complexity:98.4
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes