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Citric acid is a commonly used preservative and food additive that is widely used in food and beverages to extend shelf life. Studies have shown that Citric acid can induce apoptosis of HaCaT cells and lead to cell cycle stagnation in G2/M phase and S phase. It triggers oxidative damage in the liver by reducing antioxidant enzyme activity and exhibits renal toxicity in mice.
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CAS No. : | 77-92-9 |
Formula : | C6H8O7 |
M.W : | 192.12 |
SMILES Code : | O=C(CC(C(O)=O)(O)CC(O)=O)O |
MDL No. : | MFCD00011669 |
InChI Key : | KRKNYBCHXYNGOX-UHFFFAOYSA-N |
Pubchem ID : | 311 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P304+P340+P312-P305+P351+P338-P337+P313-P403+P233-P405-P501 |
* 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 |
---|---|---|
95.3% | Stage #1: at 80℃; for 3 h; Inert atmosphere Stage #2: at 130℃; |
Step 1, Preparation of choline-based acidic ionic liquid: 0.5mol choline chloride was heated under agitation flask was added 500mL, 0.25mol of citric acid was added, under a nitrogen atmosphere, the conditions of temperature 80 3h, after cooling to give choline-based acidic ionic liquid;Step 2, the esterification reaction: to a stirred with a mechanical, a thermometer, a reflux condenser and a four-necked flask was added 1.0mol trap n-butanol and a step in the choline-based acidic ionic liquid was heated to reflux with stirring the reaction water was separated from the trap, the reaction of the reaction to dryness stopped when re-entering the trap, choline chloride precipitates from the reaction system; the stirring was heated at reflux temperature of 130 , the stirring rate to 1000rpm;Step 3, separated choline chloride: The reaction system of Step II reaction was filtered to obtain a solid product and a liquid phase of choline chloride;Step 4, tributyl citrate purification: step 3 of the liquid product was subjected to atmospheric distillation, and then using mass concentration of 8percent NaHCO3Mass concentration of the solution or NaOH solution (also can be mass concentration of 1percent to 3percent of 1percent to 5percent Na2CO3Alternatively the solution pH) after the residue was washed atmospheric distillation residue to a value of 6, followed by activated carbon was added to the residue decolorized after washing, the activated carbon was removed by filtration, and then the residue was distilled under reduced pressure after filtration, the pressure is 260 Pa, the fraction collected 197 ~ 200 obtain tributyl citrate; the atmospheric distillation temperature of 119 deg.] C; mass of the activated carbon was 5.0percent by mass of citric acid in step a. |
94.1% | at 95 - 143℃; for 6.33333 h; | A 1 L four-necked flask equipped with a stirrer, thermometer, condenser and distillate receiver was charged with 192.0 g (1.0 mole) of anhydrous citric acid, 267.0 g (3.6 moles) of butanol and 1.9 g of sulfuric acid. The mixture was heated to 95°C over a period of 20 minutes while being stirred at atmospheric pressure. While recovering butanol and water generated as by-products of esterification in the receiver, stirring was continued for 3 hours until the reaction temperature reached 105°C. Subsequently, while recovering butanol and water generated as by-products of esterification in the receiver, 222.0 g (3.0 moles) of additional butanol was added at a reaction temperature of 101 to 143°C over a period of 3 hours to complete the reaction. After the completion of the reaction, the reaction product was cooled to 60°C, and at the same temperature (60°C), neutralized by adding sodium carbonate in an amount corresponding to twice the acid value of the reaction product (i.e., 2.0 g) and 120.0 g of water. Subsequently, the organic layer was washed with 120.0 g of water and heated to 120°C. Excess butanol was recovered until the pressure reached about 4 kPa, and steam distillation was performed at the same pressure at 120°C for 1 hour to remove low-boiling components from the reaction product, to thereby obtain 329.0 g of a colorless transparent liquid. The yield was 94.1percent and the acid value of the product was 0.025 (mg KOH/g). |
84.4% | With toluene-4-sulfonic acid In toluene at 90 - 110℃; for 4 h; | With a stirrer,Trap,Snake-shaped condenser,Necked flask equipped with a stirrer and a thermometer, 3.6 mol (266.4 g) of n-butanol was added,Citric acid 0.6 mol (210 g),P-toluenesulfonic acid (9.53 g)Toluene 50 ml.During heating from 90 ° C to 110 ° C,From the first drop of water began to reflux for 4 hours.During the reaction, the lower water layer of the water separator was continuously released and measured with a graduated cylinderWater quantity.After the esterification reaction, the excess toluene and ethanol were distilled off under reduced pressure,The reaction product is then distilled under reduced pressure to give tributyl citrate.After completion of the reaction,The product esterification rate was 96.3percentThe yield of tributyl citrate was 84.4percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.5 g | Stage #1: With hydrogenchloride In water; isopropyl alcohol for 5 h; Reflux Stage #2: at -5 - 10℃; for 10 h; |
1) 20 g of raw material (formula I) was added to the three-necked flask, 180 ml of isopropyl alcohol was added, dissolved by stirring, 50 ml of hydrochloric acid was added, and the mixture was heated under reflux for 5 hours. HPLC to monitor the E isomer greater than 35percent (HPLC Figure 1), cooled to room temperature crystallization 2h, Filtration, filter cake can be recycled, the filtrate by adding 120ml of water, if solid, filter, take the filtrate, adjust the pH to sodium with sodium hydroxide, There is a solid precipitation, extracted with ethyl acetate to the organic layer without obvious color, pure water to weak alkaline, Dried over anhydrous sodium sulfate and filtered to dryness to give 10 g of an oily substance, i.e., a mixture of Z-tamoxifen and e-tamoxifen, with an E isomer content greater than 65percent (HPLC Figure 2); 10 ml of the above sample was added with 10 ml of acetone. After stirring and stirring, 5 g of citric acid was added, stirred and dissolved, cooled at -5-10 ° C for 10 h, The filter cake was washed with acetone to give 12 g of a mixture of tamoxifen citrate and tamoxifen citrate (E isomer content greater than 70percent) (HPLC Figure 3); Take the above 12g solid, add 60ml of water and 12ml of ethanol, dissolved in activated carbon after decolorization 0.5h, hot filter, the filtrate -5-25 ° C cooling crystallization, Filtration, filter cake with acetone beating washing, drying, 8g E-tamoxifen citrate (content greater than 98.5percent, HPLC shown in Figure 4); according to the above method for secondary recrystallization, So that 7.5gE-tamoxifen citrate (content of more than 99.5percent, HPLC Figure shown in Figure 5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; at 55 - 60℃; for 4.0h; | One mole of ferrous oxide is reacted with two moles of sodium glycinate in the presence of citric acid in an aqueous solution to form <strong>[20150-34-9]ferrous bisglycinate</strong>. The <strong>[20150-34-9]ferrous bisglycinate</strong> is further reacted in a 1:1 molar ratio with citric acid to form <strong>[20150-34-9]ferrous bisglycinate</strong> citric acid chelate. Specifically, two moles of sodium glycinate (194.1 g) were dissolved in one liter of 0.5 M citric acid, and the mixture was brought to 55-60° C. Next, 1.0 mole (71.8 g) of ferrous oxide was added to the mixture, and the mixture was allowed to react for 1 hour forming <strong>[20150-34-9]ferrous bisglycinate</strong>. Next, one mole of citric acid (192.1 g) was added to the reaction mixture. After a 4 hour reaction time, the composition was cooled 40° C. and spray dried to obtain about 394.0 g of <strong>[20150-34-9]ferrous bisglycinate</strong> citrate at 100percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With sodium chloride; sodium t-butanolate; In tetrahydrofuran; | Example 3 4-(2-BROMO-PHENYL)-4-CYANO-BUT-3-ENOIC ACID METHYL ESTER A solution of 2-bromo-phenylacetonitrile (6.62 mL, 51.0 mmol) and methyl-3-methoxyacrylate (5.32 mL, 49.5 mmol) in tetrahydrofuran (10 ml) was added to a suspension of sodium tert-butoxide (5.05 g, 51.0 mmol) in tetrahydrofuran (70 mL) at 0° C. over 10 minutes under a stream of nitrogen. The reaction mixture was warmed to room temperature and after 15 minutes diluted with methyl tert-butyl ether (240 mL). To the mixture was added 0.2 N aqueous citric acid until the aqueous layer had a pH of 2 (80 mL). The organic layer was separated and washed with a saturated aqueous solution of sodium chloride (2*80 mL), dried over anhydrous sodium sulfate, filtered through a pad of Celite and silica (4:1) and concentrated in vacuo to provide 4-(2-bromo-phenyl)-4-cyano-but-3-enoic acid methyl ester as a pale yellow oil (13.8 g, 96percent). Major isomer 1H NMR (400 MHz, CDCl3) delta7.59 (dd, 1H, J =7.6, 1.2), 7.57-719 (m, 3H), 6.71 (t, 1H, J=7.1), 3.71 (s, 3H), 3.61 (d, 2H, J=7.1); 13C NMR (100 MHz, CDCl3) delta169.7, 144.4, 133.7, 131.4, 131.1, 128.3, 122.5, 118.1, 117.3, 115.3, 52.7, 36.6; IR (ATR, neat) 1737, 1434, 1319, 1199, 1171, 1026, 755 cm-1. Minor isomer 1H NMR (400 MHz, CDCl3) delta7.61 (dd, 1H, J=7.6, 1.0), 7.57-7.19 (m, 3H), 6.9 (t,1H, J=7.5), 3.64 (s, 3H), 3.06 (d, 2H, J=7.5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;palladium dihydroxide; In N-methyl-acetamide; methanol; acetonitrile; | EXAMPLE 24 (S)-3-[(2S,3R,4R,5S)-5-(O-benzyl-L-seryl)amino-2,3,4 6-tetrahydroxyhexanoyl]amino-3-phenylpropionic acid To a solution of O-benzyl-N-benzyloxycarbonyl-L-serine (329 mg) in acetonitrile (5 ml) were added N-hydroxysuccinimide (115 mg) and N,N'-dicyclohexylcarbodimide (206 mg) at room temperature and the mixture was stirred at room temperature for 3 hours. The formed insoluble solid was filtrated off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dimethylformamide (5 ml), followed by addition of triethylamine (0.139 ml) and diphenylmethyl (S)-3-[(2S,3R,4R,5S)-5-amino-2,3,4,6-tetrahydroxyhexanoyl]amino-3-phenylpropionate hydrochloride (545 mg) at room temperature and stirred at room temperature for 15 hours. To the mixture was added 10% aqueous citric acid solution and the whole was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine respectively and dried over anhydrous sodium sulfate. Removal of the organic solvent gave a residue, which was subjected to flush silica gel column chromatography, followed by elution with methanol-ethyl acetate (1:20). The effective fractions were combined and concentrated under reduced pressure. The residue was dissolved in methanol (30 ml) and stirred at room temperature with palladium hydroxide on carbon (100 mg) under hydrogen atmosphere(3-4 atm) at room temperature for 6 hours. After filtration, the filtrate was concentrated under reduced pressure to give a residue, which was passed through a column of DIAION CHP-20P (Mitsubishi kasei corporation), followed by elution with water-acetonitrile. The effective fractions were combined and concentrated under reduced pressure. The residue was recrystallized from methanol-diethylether to afford the title compound (97 mg). 1H-NMR(DMSO-d6) delta: 2.55-2.90(2H,m), 3.20-5.40(10H,m), 4.50(2H,s), 7.10-7.50(10H,m), 7.84(1H,d,J=8.8 Hz), 8.29(1H,d,J=11.4 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
480 mg (100%) | With triethylamine; In dichloromethane; ethyl acetate; | Step A: 2(R)-t-Butoxycarbonylamino-3-(t-butoxy)-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide To a solution of 200 mg (1.13 mmol) of 3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Example 1, Step B) in 8 mL of dry methylene chloride was added 0.206 mL (1.48 mmol) of triethylamine, 553 mg (1.25 mmol) of <strong>[248921-66-6]BOC-D-serine t-butyl ether</strong> followed by 602 mg (1.36 mmol) of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate. The reaction mixture was stirred at room temperature for 2 hours then diluted with 100 mL of ethyl acetate, washed with 25 mL of 5% aqueous citric acid, 25 mL of saturated sodium bicarbonate and 25 mL of brine. The organic layer was dried over magnesium sulfate, filtered and the solvents removed under vacuum. The residue was purified by flash chromatography on silica gel, eluding with ethyl acetate/hexane (55:45) to afford 480 mg (100%) of the product as a white foam. 1 H NMR (200 MHz,CDCl3): 1.20 (s,9H), 1.47 (s,9H), 1.92 (m,1H), 2.55-3.02 (m,3H), 3.38 (t,8 Hz,1H), 3.78 (m,1H), 4.15 (m,1H), 4.52 (m,1H), 5.45 (s,1H), 7.00 (m,1H), 7.10-7.35 (m,3H), 7.68 (d,4 Hz,1H), 8.05 (s,1H). FAB-MS: calculated for C22 H33 N3 O5 419; found 420 (M+H,20%), 426 (M+Li,40%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine; In ethyl acetate; N,N-dimethyl-formamide; | 1. t-Butyloxycarbonyl-glycyl-L-aspartic acid dibenzyl ester t-Butyloxycarbonyl-glycine (7.1 g) was dissolved in ethyl acetate (50 ml), cooled to -10 to -15 C. with stirring and treated with N-methylmorpholine (5.6 ml) followed by isobutyl chloroformate (5.18 ml). The mixture was stirred at -15 C. for 10 minutes. Meanwhile, L-aspartic acid dibenzyl ester p-tosylate salt (2.1 g) was dissolved in dimethyl formamide (80 ml), cooled to -10 C. and neutralized by adding N-methylmorpholine (5.6 ml). This solution was added to the above solution of the preformed mixed anhydride and the reaction mixture allowed to warm slowly to room temperature with stirring over 3 hours. The reaction mixture was then diluted with ethyl acetate (300 ml) and the solution washed with brine (twice) followed by 4% aqueous sodium bicarbonate, water, 5% aqueous citric acid and finally with water to neutrality. The organic phase was dried (magnesium sulfate) and then evaporated to an oil. Yield: 20 g. The product was homogeneous by TLC (System: chloroform:methanol:acetic acid, 360:32:8; Rf =0.8). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In 1,4-dioxane; | A. N-boc-S-trityl-cysteine, dicyclohexylammonium salt (XX) To a solution of S-trityl cysteine (see Hiskey and Adams, J. Org. Chem., 30:1340, (1965)) (36.3 g, 0.10 mol) in dioxane (200 ml) and 1M aqueous NaOH (100 ml, 0.10 mol) was added di-t-butyl carbonate (25.36 g, 0.12 mol). The resulting opaque solution became warm and effervesced and the pH fell from 12 to 8 over one hour. After stirring for 90 min, 50percent aqueous citric acid (40 ml) was added and the resulting mixture (pH 4) was extracted with ether. The ether was washed with water, then saturated brine, dried (MgSO4), filtered and evaporated to give N-BOC-S-(triphenylmethyl)-cysteine as an oil. Half of this material was dissolved in ether (200 ml) and treated with dicyclohexylamine (10 ml, 50 mmol) to give compound (XX) as a white precipitate which was filtered off, washed with ether and dried (25.1 g, 78percent), mp 205°-207°. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In ethyl acetate; | 3 M Aqueous NaOH (400 mL) and iodine flakes (35.3 g, 139 mmol) were added to the solution. After stirring at room temperature for 2 hours, the reaction mixture was neutralized to pH=6 with 20% aqueous citric acid, causing the dark color to change to light green. Saturated aqueous sodium thiosulfate (~400 mL) was added to the solution, causing the color to change from green to yellow, and the solution extracted with ethyl acetate (3*1000 mL). The combined organic extracts were dried over sodium sulfate, suction filtered through a coarse frit, and concentrated to a green sludge which was then redissolved in ethyl acetate (500 mL), filtered through a Celite pad, and concentrated to a green solid. Purification by silica gel chromatography (25% ethyl acetate in hexanes) yielded 5-Chloro-3-iodo-1H-indazole 1a (14.18 g, 44% from 5-amino-1H-indazole) as an off-white solid: mp=198-199 C.; Rf=0.53 (50% ethyl acetate/hexanes); 1H NMR (DMSO-d6) delta 7.44 (m, 2H), 7.60 (d, 1H, J=8.7 Hz), 13.68 (s, 1H). Anal. (C7H4C11N2) C, H, N. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; | EXAMPLE 2; EPO <DP n="10"/>Synthesis of Citric Acid Addition SaltThe citric acid addition salt is prepared from N-ethyl-N'-[2-methoxy-4-(5-methyl-4-[(lS)- l-pyridin-3-ylbutyl]amino}pyrimidin-2-yl)phenyl]urea by the addition of 0.66 equivalents of a solution of citric acid in methanol to the free base dissolved in methanol. The methanol is removed in vacuo and the resulting solid triturated with ether and petroleum spirit.The crystal form of N-ethyl-N'-[2-methoxy-4-(5-methyl-4-[(lS)-l-pyridin-3- ylbutyl]amino}pyrimidin-2-yl)phenyl]urea citrate salt is characterised as a pale yellow solid and is not hygroscopic. The structure was confirmed by 1H- and 13C- nuclear magnetic resonance spectroscopy and mass spectrometry.1H-n.m.r. (DMSO-d6) deltatheta.93 (t, 3H, J = 7.2 Hz), 1.06 (t, 3H, J= 7.2 Hz), 1.23-1.37 (m, IH), 1.41-1.54 (m, IH), 1.73-1.84 (m, IH), 1.96-2.08 (m, IH), 2.12 (s, 3H), 2.64 and 2.74 (AB quartet, 2.6H, J = 15.3Hz), 3.07-3.18 (m, 2H), 3.93 (s, 3H), 5.26-5.34 (m, IH), 6.91 (t, IH, J = 5.4 Hz), 7.10 (d, IH, J = 7.2 Hz), 7.32 (ddd, IH, J= 7.8, 4.8, 0.6 Hz), 7.74-7.77 (m, 2H), 7.85-7.89 (m, IH), 7.97-7.98 (m, 2H) 8.15 (d, IH, J= 8.4 Hz), 8.38 (dd, IH, J = 4.8, 1.8 Hz), 8.73 (d, IH, J= 1.8 Hz).13C-n.m.r. (DMSO-d6) 513.5, 13.6, 15.1, 19.3, 33.8, 37.9, 42.7, 52.1, 55.5, 72.2, 108.9, 111.4, 116.7, 120.0, 123.3, 130.4, 131.3, 133.7, 140.1, 146.6, 147.6, 148.4, 152.9, 154.7, 159.8, 160.1, 171.1, 174.6.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[0184] The shampoo compositions illustrated in the following Examples illustrate specific embodiments of the shampoo compositions of the present invention, but are not intended to be limiting thereof. Other modifications can be undertaken by the skilled artisan without departing from the spirit and scope of this invention. These exemplified embodiments of the shampoo composition of the present invention provide enhanced conditioning benefits to the hair. [0185] The shampoo compositions illustrated in the following Examples are prepared by conventional formulation and mixing methods, an example of which is set forth hereinbelow. All exemplified amounts are listed as weight percents and exclude minor materials such as diluents, preservatives, color solutions, imagery ingredients, botanicals, and so forth, unless otherwise specified. [0186] The compositions illustrated in the examples were prepared in the following manner (all percentages are based on weight unless otherwise specified). [0187] For each of the compositions, 6-9% of ammonium laureth-3 sulfate, P43 oil, PureSyn6 oil, cationic polymers, 0-1.5% Ammonium Xylene Sulfonate, and 0-5% water was added to a jacketed mix tank and heated to about 74 C. with agitation to form a solution. Citric Acid, Sodium Citrate, Sodium Benzoate, Disodium EDTA, Cocamide MEA and 0.6-0.9% Cetyl alcohol, were added to the tank and allowed to disperse. Ethylene glycol distearate (EGDS) was then added to the mixing vessel, and melted. After the EGDS was well dispersed (after about 10 minutes) preservative was added and mixed into the surfactant solution. This mixture was passed through a heat exchanger where it was cooled to about 35 C. and collected in a finishing tank. As a result of this cooling step, the ethylene glycol distearate crystallized to form a crystalline network in the product. [0188] Separately about 20% of the water was heated to about 74 C. and the remainder of the Cetyl Alcohol, Stearyl Alcohol, and the Cationic Surfactant were added to it. After incorporation, this mixture was passed through a heat exchanger where it was cooled to about 35 C. As a result of this cooling step, the Fatty Alcohols and surfactant crystallized to form a crystalline gel network. [0189] These two premixes are the mixed together and the remainder of the surfactants, perfume, Dimethicone, Sodium Chloride or Ammonium Xylene Sulfonate for viscosity adjustment and the remainder of the water were added with ample agitation to insure a homogeneous mixture. [0190] Preferred viscosities range from about 5000 to about 9000 centipoise at 27 C. (as measured by a Wells-Brookfield model RVTDCP viscometer using a CP-41 cone and plate at 2/s at 3 minutes). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLES [0184] The shampoo compositions illustrated in the following Examples illustrate specific embodiments of the shampoo compositions of the present invention, but are not intended to be limiting thereof. Other modifications can be undertaken by the skilled artisan without departing from the spirit and scope of this invention. These exemplified embodiments of the shampoo composition of the present invention provide enhanced conditioning benefits to the hair. [0185] The shampoo compositions illustrated in the following Examples are prepared by conventional formulation and mixing methods, an example of which is set forth hereinbelow. All exemplified amounts are listed as weight percents and exclude minor materials such as diluents, preservatives, color solutions, imagery ingredients, botanicals, and so forth, unless otherwise specified. [0186] The compositions illustrated in the examples were prepared in the following manner (all percentages are based on weight unless otherwise specified). [0187] For each of the compositions, 6-9% of ammonium laureth-3 sulfate, P43 oil, PureSyn6 oil, cationic polymers, 0-1.5% Ammonium Xylene Sulfonate, and 0-5% water was added to a jacketed mix tank and heated to about 74 C. with agitation to form a solution. Citric Acid, Sodium Citrate, Sodium Benzoate, Disodium EDTA, Cocamide MEA and 0.6-0.9% Cetyl alcohol, were added to the tank and allowed to disperse. Ethylene glycol distearate (EGDS) was then added to the mixing vessel, and melted. After the EGDS was well dispersed (after about 10 minutes) preservative was added and mixed into the surfactant solution. This mixture was passed through a heat exchanger where it was cooled to about 35 C. and collected in a finishing tank. As a result of this cooling step, the ethylene glycol distearate crystallized to form a crystalline network in the product. [0188] Separately about 20% of the water was heated to about 74 C. and the remainder of the Cetyl Alcohol, Stearyl Alcohol, and the Cationic Surfactant were added to it. After incorporation, this mixture was passed through a heat exchanger where it was cooled to about 35 C. As a result of this cooling step, the Fatty Alcohols and surfactant crystallized to form a crystalline gel network. [0189] These two premixes are the mixed together and the remainder of the surfactants, perfume, Dimethicone, Sodium Chloride or Ammonium Xylene Sulfonate for viscosity adjustment and the remainder of the water were added with ample agitation to insure a homogeneous mixture. [0190] Preferred viscosities range from about 5000 to about 9000 centipoise at 27 C. (as measured by a Wells-Brookfield model RVTDCP viscometer using a CP-41 cone and plate at 2/s at 3 minutes). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19% | With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; | Step Atert-butyl (4-fluoro-1,3-dihydro-2H-isoindol-2-yl)methylcarbamate3-Fluoro-ortho-xylene (1.99 g, 16.03 mmol), N-bromosuccinimide (6.98 g, 39.22 mmol) and benzoyl peroxide (0.24 g) were added to carbon tetrachloride (60 ml), and the mixture was heated under reflux for 45 min.The reaction mixture was cooled, diluted with hexane, and the insoluble material was filtered off.The obtained solution was concentrated under reduced pressure.Using the obtained oil, the reaction was performed according to the method of Reference Example 17, step B.After completion of the reaction, 10percent aqueous citric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate-hexane=1:1 mixed solvent, washed with water, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate.The insoluble material was filtered off, and the solution was concentrated under reduced pressure.The obtained oil was purified by silica gel column chromatography (ethyl acetate-hexane) to give the title compound (826 mg, yield 19percent) as a pale-yellow oil.1H-NMR (300 MHz, CDCl3); delta(ppm) 1.41 (s, 9H), 3.09 (s, 3H), 4.47 (s, 2H), 4.48 (s, 2H), 6.87 (t, J=8.6, 1H), 6.94 (d, J=7.2, 1H), 7.1-7.2 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.05 g | In dichloromethane; water; | At -50C, 4-(N,N-dimethyl)amino-2(R,S)-difluoromethylbutyric acid hydrochloride (2.0 g), 4-N,N-dimethylpyridine(1.8 g), and dicyclohexylcarbodiimide (2.1 g) were added to acetonitrile (150 ml). Paclitaxel (1.6 g) was added, andthe reaction was carried out for 18 hours. Upon completion of the reaction, the solvent was removed by evaporationunder reduced pressure, and the residue was dissolved in dichloromethane (100 ml). The DCM layer was washed witha saturated aqueous sodium chloride solution (the pH of which was adjusted to about 3.0 with hydrochloric acid), driedover anhydrous sodium sulfate, and filtered. DCM was removed by rotary evaporation, and the residue was dissolvedin a little acetone. Isopropyl ether was added for crystallization, and 2?-O-[4-N,N-dimethylamino-2(R,S)-difluoromethylbutyryl]paclitaxel hydrochloride (1.2 g) was obtained. The hydrochloride salt was dissolved in dichloromethane (100 ml).The dichloromethane layer was washed with an aqueous solution (pH = 3) of citric acid and <strong>[68-04-2]sodium citrate</strong>, dried overanhydrous sodium sulfate, and filtered. The solvent was removed by rotary evaporation, and 2?-O-[4-N,N-dimethylamino-2(R,S)-difluoromethylbutyryl] paclitaxel citrate (1.05 g) was obtained.ESI-MS m/z [M+H]+ :1017. 54. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 25℃; for 12h; | 202.7 mg of the compound of the formula (I) was suspended in 10 mL of acetonitrile, 119.0 mg of citric acid was added and the mixture was stirred at room temperature (25 ± 2C) for 12 hours, and the solid was collected. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.58% | Ethyl 2,4,5-trifluorobenzoylacetate (20.0 g, 0.081 mol) was added to a 250 mL reaction flask.Triethylorthoformate (21.6 mL, 0.130 mol), acetic anhydride (32.5 mL, 0.344 mol), stirring,Heating was started and the temperature of the feed was raised to 130 C. for 4.0 hours.After the reaction was completed, the solvent was distilled off under reduced pressure to obtain an oily liquid.Add 70 mL of N-methylpyrrolidone to make the oily liquidThe solution was dissolved, <strong>[247069-27-8]3,5-difluoro-2,6-diaminopyridine</strong> (13.8 g, 0.095 mol) was added, and the feed solution was warmed to 50C.Stir and stir for 1.5h. After the addition of anhydrous lithium chloride (6.12 g, 0.146 mol), DBU (11.37 g, 0.075 mol) was added, and the reaction temperature was controlled at 35 C. for 2.0 h.3-Hydroxyazetidine hydrochloride (8.45 g, 0.077 mol) was added, DBU (26.82 g, 0.176 mol) was slowly added, and the temperature was 35 C. for 2.5 h.After the reaction is complete, transfer to a 500 mL reaction flask and add 25 mL of ethyl acetate.Slowly add 145 mL of 10% citric acid solution.After the addition was completed, the temperature was adjusted to 20C, and the crystals were crystallized for 4.0 hours. The crystals were collected, and the mixture was collected by suction filtration. The cake was collected and dried in an oven at 60C to obtain 38.35 g of the intermediate I. The yield was 93.58%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75%Spectr.; 9%Spectr. | With hydrogen; In water; at 250℃; under 51755.2 Torr; for 0.833333h; | 420 mg of citric acid monohydrate was dissolved in 20 mL of water, 0.5 mol% of Pd/C (catalyst in powder form) was added and the reactor was flushed 3 times with N2 and 3 times with H2. Then the reactor was loaded with 69 bar H2 and heated to 250C for a period of 50 min . This reaction resulted in the production of mainly methylsuccinic acid (75%) and propane-l,2,3-tricarboxylic acid (9%). Using Pd/C as the catalyst, methylsuccinic acid remains the primary product for the reaction in water at 250C and a pressure of 69 bar H2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48%Spectr.; 8%Spectr. | With hydrogen; In water; at 225℃; under 3000.3 Torr; for 0.67h; | General procedure: 42 mg of citric acid monohydrate was dissolved in 2 mL of water; 0.8 eq. of NaOH was added in some of the reactions. 4 mol% of active metal (catalyst in powder form) was added and the reactor was flushed 6 times with N2. Then the reactor was loaded with 4 bar H2 and heated to 225C for a period of 6 h or 40 min. The conversion of citric acid was >99% in all cases. The highest yields in these conditions (67-85%) were obtained with Pd and Rh catalysts. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.51 g | Weighing 6.10g of fangchinolinbase,2.80 g of 2-methoxy-5-trifluoromethylbenzyl chloride and 0.50 g of potassium hydroxide were dissolved in 250 mL of methanol in a 500 mL three-necked flask, stirred and heated to 50 C, and stirred for 72 h.HPLC was used to detect the total reaction of the fangchinolinbase, the solvent was distilled off under reduced pressure, and the mixture was cooled to room temperature, filtered, and the reaction was separated and purified by HPLC.The filtrate was added with 20% citric acid (pH=7.5) and heated to stir for 4 h, and cooled to room temperature.Steam under reduced pressure until the liquid volume is reduced to50mL, crystallized at room temperature for 8h, filtered, and the solid was dried at 60 C for 4 h.That is, 4.51 g of a product as a pale yellow powder. The melting point of the desired product: 201.5-203.4 C, TOF-HRMS: M/e (1289.2344), molecular formula: C68H65O13N2F9,That is, the compound III209 in Table 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.62 g | Weighing 6.10g of <strong>[436-77-1]fangchinoline</strong>, 2-methoxy-5-trifluoromethylbenzyl chloride 2.26g and potassium hydroxide 0.50g dissolved100 mL of methanol was placed in a 500 mL three-necked flask and heated to 50 C with stirring.The reaction was stirred for 72 hours, and the total reaction of the <strong>[436-77-1]fangchinoline</strong>base was detected by TLC, and the mixture was filtered at room temperature.TLC tracks the separation and purification process of the reaction and the product,20% citric acid neutralized to neutralpH=7.1,Steaming under reduced pressure until the volume of the liquid is reduced to 1/4, standing at room temperature for 8 hours, filtering, and drying the solid at 60 C for 4 h, ieThe product was obtained as a pale yellow powder, 2.62 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In isopropyl alcohol; for 1h;Reflux; | Dissolving the free substance of carbaplatin in a 6-fold ratio of isopropanol solution,After heating to reflux to dissolve, add 1.2 times the crude moles of anhydrous citric acid.Stir and dissolve for 1 h. After cooling to room temperature, transfer to a cold water bath at 0-5 C.A white solid precipitated, and continued to crystallize for 5 h, filtered, and the filter cake was washed with isopropanol.Take out the filter cake and dry it in a vacuum drying box at 60 C under reduced pressure for 24 hours to obtain crude carbatine citrateYield: 90%, HPLC content: 99.2%Dissolve the crude product in 6 times the amount of isopropanol solution, add 0.02 times the crude amount of medicinal charcoal, 0.03 times the amount of insurance powder and heat to reflux and stir. Continue stirring for 1 hour, filter while hot, filter off the medicinal charcoal and insurance. Powder solid, collect mother liquor, cool down and recrystallize. When the temperature is lowered to 60 , add seeds of carbaplatin citrate, white solid precipitates, cool down to 0-5 , continue to stir and crystallize for 5h, filter, and wash with isopropyl alcohol. the filter cake, the filter cake was removed and dried under reduced pressure to obtain the final product 24h <strong>[123441-03-2]rivastigmin</strong>e citrate, 88% yield in a vacuum oven 60 , HPLC content of 99.8%. |
Tags: Citric acid | Carboxylic Acids | Aliphatic Chain Hydrocarbons | Alcohols | Ixazomib Citrate | Inflammation Model | Drug Standard | Bile Acid | Fungicide | Steroids | Antineoplastics | Pesticide Composition | Organic Building Blocks | Animal Modeling Agents | Drug Analysis | Other Inhibitors/Agonists | 77-92-9
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