Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 617-45-8 | MDL No. : | MFCD00063083 |
Formula : | C4H7NO4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CKLJMWTZIZZHCS-UHFFFAOYSA-N |
M.W : | 133.10 | Pubchem ID : | 424 |
Synonyms : |
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.5 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 5.0 |
Num. H-bond donors : | 3.0 |
Molar Refractivity : | 27.59 |
TPSA : | 100.62 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -9.87 cm/s |
Log Po/w (iLOGP) : | -0.14 |
Log Po/w (XLOGP3) : | -3.89 |
Log Po/w (WLOGP) : | -1.13 |
Log Po/w (MLOGP) : | -3.59 |
Log Po/w (SILICOS-IT) : | -1.49 |
Consensus Log Po/w : | -2.05 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 3.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | 1.98 |
Solubility : | 12800.0 mg/ml ; 96.3 mol/l |
Class : | Highly soluble |
Log S (Ali) : | 2.37 |
Solubility : | 31400.0 mg/ml ; 236.0 mol/l |
Class : | Highly soluble |
Log S (SILICOS-IT) : | 1.31 |
Solubility : | 2730.0 mg/ml ; 20.5 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.8 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P233-P260-P261-P264-P271-P280-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P332+P313-P337+P313-P340-P362-P403-P403+P233-P405-P501 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
95.54% | With hydrogen;1% Pd/C; In water; at 90℃;Reflux; | 25 g of aspartic acid was placed in a 500 ml round-bottom flask, 60 ml of formaldehyde aqueous solution (concentration: 37%), 200 ml of water and 8 g of Pd/C were added sequentially. The air in the flask was displaced by hydrogen, the flask was placed under the hydrogen atmosphere and the reaction was conducted for 48 hours. After the reaction, the remaining hydrogen was displaced by nitrogen, the flask was heated to 90 C. under reflux, and Pd/C was filtered out at the high temperature to obtain a colorless aqueous solution. The colorless aqueous solution was concentrated and azeotroped with 100 ml of toluene to further remove the water. The product was dried under high vacuum, and ground by using a spatula to obtain 28.92 g of N,N-dimethylaspartic acid as a pale yellow solid (Yield: 95.54%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With thionyl chloride; at -78 - 20℃; for 16h;Product distribution / selectivity; | 4.3.7 2-aminobutane-l,4-diol (ICEC0320)NH2[00277] DL-aspartic acid (13.3 g, 100 mmol) was stirred in EtOH (200 mL) and cooled to -78 0C. SOCl2 (15 mL, 210 mmol) was added drop-wise and the reaction mixture was allowed to warm to rt and stirred for additional 16 h. The solvent was evaporated and the residue was re-dissolved in EtOAc (100 mL). The organic layer was washed with brine (100 mL) and the aqueous layer was extracted with EtOAc (3 x 50 mL). The solvent was evaporated to give 12.75 g, 67% of the corresponding diester, which was used without further purification (Lakanen et al., J. Med. Chem., 1995, 38, 2714).; 2,2,3,3,10,10,ll,ll-octamethyl-4,9-dioxa-3,10-disiladodecan-6-amine (ICEC0321)[00283] DL-aspartic acid (13.3 g, 100 mmol) was stirred in EtOH (200 mL) and cooled to -78 0C. SOCl2 (15 mL, 210 mmol) was added drop-wise and the reaction mixture was allowed to warm to rt and stirred for additional 16 h. The solvent was evaporated and the residue was re-dissolved in EtOAc (100 mL). The organic layer was washed with brine (100 mL) and the aqueous layer was extracted with DCM (3 x 50 mL). The solvent was evaporated to give 12.75 g of the corresponding diester, which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In 1,4-dioxane; water; at 0 - 20℃; | EXAMPLE 4 N-(tert-butoxycarbonyl)-DL-aspartic acid DL aspartic acid acid (1 g) was dissolved in 20 mL of dioxane/water 1:1 and 4.15 mL of triethylamine was added. The mixture was cooled to 0 C. and 2.4 g of di-tert-butyl dicarbonate added. The solution was left at room temperature overnight. The suspension was concentrated and extracted with ethyl acetate and water. The aqueous extract was acidified with 5% aq. NaHSO4 and then extracted with AcOEt three times. The organic extracts were dried over anh. sodium sulfate and the solvent evaporated under vacuum to provide 1.53 g of the title compound. 1H NMR (400 MHz, DMSO-D6) delta ppm 1.36 (s, 9 H) 2.45-2.57 (m, 1 H) 2.60-2.72 (m, 1 H) 4.19-4.31 (m, 1 H) 7.01 (d, J=8.50 Hz, 1 H) 12.45 (bs, 2 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With camphor-10-sulfonic acid; at 60℃; for 24h; | Aspartic acid (303.1 mg, 2.28 mmol) was dissolved in benzyl alcohol (1 mL), was added a CSA (2.0 eq, 1.05 g), was allowed to stir to react for 24 hours at 60 C.. After completion of the reaction, saturated aqueous sodium hydrogen carbonate solution to the reaction mixture was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, and subjected to concentration under reduced pressure. The residue was purified by silica gel chromatography (hexane: ethyl acetate = 2: 1 ? 1: 1 ? 1: 2 ? 1: 4) to give the corresponding benzyl ester (10a) (391.0 mg, 1.25 mmol, 55%) the Obtained. CompoundObject 10a (391.0 mg, 1.25 mmol) was dissolved in ethyl formate (20 mL), p-TsOH (0.1 eq, 23.7 mg) was added and allowed to stir to react for 41 hours at 60 . After completion of the reaction, saturated charcoal to the reaction mixtureAqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, Dried with magnesium sulfate, and after filtration, was concentrated under reduced pressure. The residue was purified by silica gel chromatographyChromatography (hexane: ethyl acetate = 1: 1) to give the corresponding formamide (10b) (277.4 mg, to obtain a 0.71 mmol, 57%). Compound 10b (277.4 mg, 0.81 mmol) and DCM (5mL) was added in, the mixture obtained PhOPOCl2 (1.5 eq, 182 muL) and pyridine (5.0 eq,0.56 mL) was added, and stirred to react at room temperature for 2 hours. After completion of the reaction, saturated diet reaction mixtureBrine was added and extracted with ethyl acetate. The organic layer, hydrochloric acid, sodium hydrogen carbonate, and saturated dietSuccessively washed with brine, and dried over magnesium sulfate, filtered, subjected to concentration under reduced pressure.The residue was purified by silica gel chromatography (hexane: ethyl acetate = 5: 1 ? 4: 1) by finePapermaking, isonitrile (10) was obtained (11.8 mg, 0.036 mmol, 5%). Yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In tetrahydrofuran; at 0℃; for 6.08333h;Heating / reflux; | This example that demonstrates how this method could be performed. 9.4 g aspartic acid, 10 ml triethyl amine and 100 ml tetrahydrofuran are transferred into a 100 ml flask fitted with a condenser and nitrogen inlet. The mixture is cooled to 0 C. and 5 g succinyl chloride is added and the mixture stirred under nitrogen atmosphere for 5 min and refluxed for 6 hours. The triethyl amine hydrochloride is filtered and the filtrate is concentrated by removing the solvent under vacuum. The residue is used directly for the subsequent reaction. The residue can be purified by chromatography on silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; at 100℃; for 0.0833333h;Microwave irradiation; | General procedure: A suspension of suitable amino acid (16-20) (1 mmol) and carbon disulfide (1 mmol, 60 mul) in a solution of NaOH (2 mmol) and water (10 ml) was reacted in a microwave reactor for 5 min at 100 C. After automated cooling chloroacetic acid (1 mmol) was added and the mixture was reacted again at 100 C for 5 min. After cooling HCl (3 ml, 6 N) was added and the reaction was finished at 120 C for 30 min. The mixture was neutralized with a saturated NaHCO3 aqueous solution, extracted with ethyl acetate (10 mL * 3) and dried over Na2SO4. After removal of the solvent under reduced pressure, the crude mixture was purified by flash chromatography using a mixture of CH2Cl2/CH3OH (90:10) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To 10 g. of the compound of formula (2a) in 150 ml. of water, 3.4 g. of aspartic acid are added and the mixture heated to 70 C., the pH being maintained at between 8 and 8.5 by the addition of a 32% aqueous sodium hydroxide solution. After 2 hours at this temperature, the reaction is completed. The pH of the mixture is then adjusted to 3 by the addition of 37% aqueous hydrochloric acid, the temperature being maintained at 70 C. The precipitated free acid is filtered, suspended in a methanol/water mixture and the pH adjusted to 9 by the addition of a 32% aqueous sodium hydroxide solution. The precipitated product is filtered and dried to yield 8.8 g. of the compound of formula (2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; polyethylene glycol 300; at 90℃; for 7h;pH 8.5 - 9.3; | 15.0 g of 4,4'-bis[(4anilino-6-chloro-1,3,5-triazin-2-yl)amino]stilbene-2,2'-disulphonic acid disodium salt are suspended in 14.0 g of polyethylene glycol 300 and 29.6 g of water. To the stirred suspension are then added 2.15 g of aspartic acid, 1.7 g of diethanolamine and 1.2 g of 50% aqueous sodium hydroxide solution. The reaction mixture is heated to 90 C. and stirring continued at this temperature for 7 hours, the pH being maintained at 8.5-9.3 by addition of 32% aqueous sodium hydroxide solution. The reaction mixture is cooled and filtered to yield a liquid formulation containing 24.6% of the fluorescent whitening agent (104), which comprises a mixture containing 39% of compound (101a), 22% of compound (104b) and 33% of compound (104c). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.9% | With phosphoric acid; nitrogen;silica gel; In diphenylether; acetone; | Example 4 To a reaction vessel equipped with a Dean-Stark trap, 30 g of aspartic acid, 150 g of diphenyl ether and 15 g of 85% phosphoric acid were charged. The mixture was stirred at 145 C. for 0.5 hour under atmospheric pressure to carry out azeotropic dehydration. The reaction became heterogeneous, bulk material was stirred and the reaction was progressed. Thereafter the Dean-Stark trap was removed from the reaction vessel, and Dean-Stark trap was removed from the reaction vessel, and a column packed with 20 g of molecular sieves 3A was mounted on the vessel so as to return the distilled solvent to the vessel after passing through the column. Further, 100 g of NMP was added to the reaction mixture, and the reaction was continued at 180 C. for 16 hours under atmospheric pressure while bubbling nitrogen gas. The water content of the solvent was 3 ppm after passing through the molecular sieves. After finishing the reaction, acetone was added to the reaction mixture. Precipitate formed was filtered, washed with acetone, successively washed with water and dried at 60 C. for 4 hours under reduced pressure of 5 mmHg and at 110 C. for 4 hours reduced pressure of 5 mmHg. Polysuccinimide thus obtained was 19.9 g (yield 90.9%). The polymer had eta of 0.24 dl/g and Mw of 60,000. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.0% | In diphenylether; | Example 2 To a reaction vessel equipped with a Dean Stark trap, 30 g of aspartic acid, 150 g of diphenyl ether and 0.6 g of magnesium oxide catalyst were charged. The resulting suspension was stirred at 190 C. for 6 hours under reduced pressure of 135 mmHg to carry out azeotropic dehydration. Thereafter the Dean-Stark trap was removed from the reaction vessel and a column packed with molecular sieves 3A was mounted on the vessel so as to return the distilled solvent to the vessel after passing through the column. The reaction was further continued at 190 C. for 15 hours under reduced pressure of 135 mmHg. The water content of the solvent was 5 ppm after passing through the molecular sieves. After finishing the reaction, the suspension was filtered, washed with acetone and dried at 110 C. for 6 hours under reduced pressure of 5 mmHg. Polysuccinimide thus obtained was 19.7 g (yield 90.0 %). The polymer had eta of 0.15 dl/g and Mw of 30,000. |
90.0% | In diphenylether; | Comparative Example 1 The reaction was carried out at 210 C. for 20 hours under atmospheric pressure by using 30 g of aspartic acid and 150 g of diphenyl ether. The suspension was filtered washed with acetone and dried at 110 C. for 6 hours under reduced pressure of 5 mmHg. Polysuccinimide thus obtained was 19.7 g (yield 90.0%). The polymer had eta of 0.074 g dl/g and Mw of 10,000. |
Example 6 Example 4 was repeated with 150 g of aspartic acid instead of 50 g. About 150 g of polysuccinimide was recovered having a nitrogen content of 14,5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In diethyl ether; at 20℃; for 24h; | First prepare a single-mouth flask (500 mL), add 100 mL of anhydrous ether, then slowly add 10 mL of concentrated H2SO4 (98%), stir vigorously while stirring, and then cool to room temperature, then add 100 mL of benzyl alcohol. After stirring, the ether was evaporated by rotary evaporation. Then, a total of 13.3 g of aspartic acid was added to the reaction flask three times. Stir the reaction at room temperature for 24 h, then add200 mL of 95% ethanol was added, and 50 mL of pyridine was added dropwise with a dropping funnel, and vigorously stirred while dropping. Then, it was frozen overnight in a refrigerator, and the solid after the reaction was stirred and dissolved at 80 C, and then filtered while hot, and the filtrate was refrigerated overnight. After the above steps, the crystal was recrystallized twice, and lyophilized to obtain pure beta-aspartic acid benzyl ester |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41.5% | Compound 1a:; To an aqueous HCI solution (5.5 N, 5OmL) was added O-Phenylenediamine dihydrochloride (9.05g, 0.05mol) and DL-aspartic acid (1Og, 0.075mol). The mixture was heated at reflux for 7Oh. After being cooled down to 25C, the suspension was filtered. The pH of filtrate was adjusted to pH~2 by slow addition of Na2CO3 solid. The precipitate was collected by filtration, washed with water and dried in vacuum oven (60C). A pale green powder (5g, 41.5%yield) was obtained. 1H NMR (CD3OD): delta 7.75-7.65 (2H, m), 7.55-7.45 (2H, m), 4.64-4.58 (1 H, m), 3.8-3.72 (2H, m). LCMS (APCI): 206(M+H+) (positive); 204 (M-H) (negative). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium methylate; | EXAMPLE 16 (N-Formyl-L-Aspartic Acid, Monosodium Salt) The reaction was run as described in Example 8 except that 0.345 gm (2.5 mmol) aspartic acid and 0.140 gm (2.5 mmol) sodium methoxide was used. The conversion of L-aspartic acid monosodium salt to N-formyl-L-aspartic acid monosodium salt was 95% as analyzed by proton NMR. (See NMR data, below.) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 20℃; for 18h;Molecular sieves 4A; | To a suspension of 4-(3-isocyanato-benzyl)-2H-phthalazin-1-one (2)(1.4 g, 4.75 mmol) in dry DCM (30 ml) in the presence of activated 4 molecular sieves (ca 2 g) was added DL-aspartic acid (0.60 g, 5.0 mmol), followed by triethylamine (10.0 mmol). The reaction was stirred at room temperature for 18 hours. The reaction mixture was then diluted with bicarbonate solution (20 ml) and the mixture filtered removing undesired urea byproduct. The aqueous phase contained the title compound and was washed with DCM (2×10 ml). The aqueous layer was then concentrated in vacuo to afford a beige solid, HPLC showed this to be a mixture of components (41 & 42). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | A solution of aspartic acid (133.1 mg, 1 mmol), N-hydroxysuccinimidyl gambogate (362 mg, 0.5 mmol) and triethylamine (0.1 mL) in anhydrous DMSO (10 mL) was stirred for 48 h. It was diluted with water (50 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layer was extracted with saturated aqueous sodium bicarbonate (20 mL). The basic aqueous layer was acidified with 1N HCl to pH=2 and was extracted with ethyl acetate (3×20 mL). The combined organic layer was dried, concentrated to give 110 mg (30%) of the title compound. 1H NMR (CDCl3): 12.80 (s) and 12.70 (s) (1H), 7.56-7.54 (m, 1H), 6.67-6.60(m, 1H), 5.56-5.52 (m, 1H), 5.47-5.43 (m, 1H), 5.22 (t, J=6.0 Hz, 1H), 5.07 (m, 1H), 4.84 (m, 1H), 3.55-3.20 (m, 8H), 3.20-2.30 (m, 5H), 1.76-1.74 (3H), 1.71-1.69 (3H), 1.65 (bs, 6H), 1.56 (s, 3H), 1.43-1.41 (3H), 1.34 (s, 3H), 1.28-1.26 (3H); MS. 744 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With thionyl chloride; at 0 - 5℃;Reflux; | Into a 100-mL round- bottom flask, was placed a solution of 2-ammosuccinic acid (3 g, 22 56 mmol, 1 00 equiv) in methanol (20 mL) This was followed by the addition of thionyl chlo?de (10 g, 8475 mmol, 3 16 equiv) dropwise with stirring at 0-50C The resulting solution was heated to reflux for 2 h in an oil bath The resulting mixture was concentrated under vacuum This resulted in 42 g (95%) of the title compound as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water;Heating / reflux; | An aqueous mixture is prepared from a diphenhydramine acid salt (the HCl salt). First, the free base of diphenhydramine HCl is prepared by adding 1.48 parts by weight of a 50% by weight sodium hydroxide solution to diphenhydramine HCl (5.4 parts by weight) and 70 parts by weight water. A molar excess of racemic aspartic acid (2.68 parts by weight) then is added. The solution is prepared by mixing these ingredients with a slight heating as needed. The noted acid salt can be isolated for later use, or can be used directly to produce taste masked granules, for example by mixing the acid salt solution with 13 parts by weight of a 23% by weight aqueous solution of polyethylene glycol (M.W. 3350) and then 6 parts macrocrystalline cellulose. The homogeneous mixture is concentrated under vacuum (Rotovap) at 65C to produce a solid granular product containing over 40% of diphenhydramine aspartate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Synthesis of [3-15N]orotic acid. [3-15N]Orotic acid was synthesized based on previous reports with some modifications.43,44 Briefly, 1.47 g of DL-aspartic acid, 1.74 g of KOH and 0.66 g of [15N2]urea were dissolved in 33.3 mL of water. The mixture was refluxed at 115 C. for 2 hr, then two portions of 0.66 g of [15N2]urea were added separately with a 2 hr interval. After 6 hr reaction, the mixture was acidified with 3 mL of concentrated HCl and allowed to stand overnight at room temperature. Precipitated ureidosuccinic acid was filtrated and recrystallized from water. Ureidosuccinic acid (0.82 g) was dissolved in 2.73 mL of 20% HCl. The mixture was evaporated to dryness on a hot plate. The resulting 5-acetic acid-hydantoin was recrystallized from water. Crystals (0.62 g) were mixed with 2.46 mL of glacial acetic acid and 0.62 g of bromine and heated at 100 C. in a sealed tube for 2 hr. Precipitated 5-carboxymethylidine-hydantoin was filtrated, recrystallized from water and 0.42 g of the product was added to 14 mL of 1 M KOH. Following 64 C. for 2 hr, the [3-15N]orotic acid was precipitated by acidification with concentrated HCl and recrystallization from water. [3-15N]orotic acid: 15N NMR (75 MHz, DMSO-d6) delta ppm 161; m/z std C5H5N2O4 (M+1) 157.026, C5H515N1N1O4 (M+1) 158.023. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.8% | Into a 1000 L enamel reactor, 300 Kg of deionized water was added in sequence.133.1Kg aspartic acid, 1.0Kg sodium iodide, start stirring,Add potassium carbonate solution (m/m = 50.0%) to adjust the pH to 9.6-9.9.After stirring at this temperature for 1.5 h, the temperature was raised to 65.0 C while the remaining potassium carbonate aqueous solution (m/m = 50.0%) was added dropwise.After 15 minutes, 285.0 Kg of aqueous chloroacetic acid solution (m/m = 70.0%) was added dropwise.The temperature control is completed at 65.0-70.0 C, about 4.0 h, and stirring is continued for 3.5 h at this temperature.Then, the temperature is raised to 90.0 C for the heat preservation reaction for 3.5 h, and the temperature is lowered to a room temperature after vacuum dehydration.Filtration, the filtrate is a N,N-bis(carboxymethyl)aspartic acid tetrapotassium saltsolution.After testing, the content of N,N-bis(carboxymethyl)aspartic acid tetrapotassium saltin the obtained mixture was 43.4%.Yield 95.8% (calculated as aspartic acid). | |
With potassium hydroxide; In water;pH ~ 10;Heating to boiling; | This Example demonstrates the synthesis of the potassium salt of Aspartatic Acid N,N-Diacetic Acid.To 13.31 grams (100 millimols) of aspartic acid, 40 grams of 5 Normal potassium hydroxide (200 millimols) was added and mixed to neutralize. Forty-one grams of potassium hydroxide 5 Normal (205 millimols) were added to 19.37 grams of chloroacetic acid (205 millimols) and mixed to neutralize. The neutralized chloroacetic acid was added to the neutralized aspartic acid and the mixture was heated to boiling.Twenty-six grams of potassium hydroxide (130 millimols) was added stepwise as needed to maintain a pH of about 10. Once the pH was stable without further addition of potassium hydroxide, the solution was heated for an extra 10 minutes at boiling temperature. The solution was then chilled in an ice bath and 11.91 grams of potassium chloride (185 millimols) precipitated which was separated by filtration and discarded. Approximately 0.97 grams of potassium chloride remained in the solution containing the potassium salt of Aspartic Acid-N,N-Diacetic Acid.Example 1 demonstrates that a very pure product is formed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.52% | In water; at 80℃; for 3h; | 10 g of aspartic acid was added to a 250 ml round-bottom flask, and 100 ml was added and stirred for 30 minutes. A formaldehyde aqueous solution (concentration: 37%, 20 ml) was added to the flask, and the reaction was conducted at 80 C. After performing the reaction for 3 hours, a yellow liquid was obtained. The yellow liquid was concentrated, azeotroped with 100 ml of toluene to further remove the water and dried under vacuum to obtain a yellow solid (10.63 g, Yield: 97.52%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 75℃; for 12h; | Example 1-2Preparation of DTPA-bis-amide-aspartic acid (L2) of Formula 1To a stirred suspension of 0.71 g (2 mmol) of DTPA-bis-anhydride in 15 mL of N,N-dimethylformamide (DMF) was added 0.53 g (4 mmol) of aspartic acid. The mixture was stirred at 75 C. for 12 hours, and the solvent was completely removed under low pressure, and the residue was dissolved in 10 mL of methanol. The solution was passed through a short column of silica gel (60 mesh) with methanol. The eluate was precipitated in 250 mL of acetone, followed by filtration. The obtained white solid product was dried under vacuum at 65 C. for 10 hours. FIG. 1(b) is a schematic diagram of the synthetic method, and the result of Maldi-TOF mass spectrometry is shown in FIG. 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; water; at 40℃; for 2.83333h; | 1.0 g of 99% TD crystal was dissolved in 10 ml ethanol, and the resulting solution was added a aqueous solution of 0.266 g aspartic acid (preferably L-aspartic acid) over 20 minutes at 40 C. while stirring, After stirring continuously for 150 minutes at this temperature, the solution was cooled to room temperature gradually, lyophilized under vacuum to afford off-white solid, m.p. 163 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; at 20℃; for 1h; | At 20C, a flask was charged with 30 mL of water, 20 g of aspartic acid, and then with 5 g of (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid under agitation. After 60 minutes of agitation, an essentially clear liquid was obtained. To the liquid was added 5% of active carbon to discolor for 30 minutes. The mixture was filtered. To the filtrate was added 200 mL of anhydrous ethanol under agitation for 1 hour to precipitate the solid. After additional 2 hours of agitation, the mixture was filtered; the solid was dried at 50C under vacuum to yield 3.7 g of (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid asparate. IR 1695 cm-1, 1628 cm-1, 1602 cm-1, 1499 cm-1; 1H-NMR (D2O) delta2.13 (2H, m), 2.70?2.89 (3H, s), 3.50?3.57 (8H, m), 3.93 (1H, q, j=4.8Hz), 6.16(1H, s), 6.57(1H, s), and 7.35(1H, d, j=12.8Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; at 20℃; for 1h; | At 20C, a flask was charged with 30 mL of water, 20 g of aspartic acid, and then with 5 g of (R)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid under agitation. After 60 minutes of agitation, an essentially clear liquid was obtained. To the liquid was added 5% of active carbon to discolor for 30 minutes. The mixture was filtered. To the filtrate was added 200 mL of anhydrous ethanol under agitation for 1 hour to precipitate the solid. After additional 2 hours of agitation, the mixture was filtered; the solid was dried at 60C under vacuum to yield 3.7 g of (R)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid aspirate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water; In ethanol; at 70℃; for 1h; | Example 257 diphenyl(asparaginate-O,N)borane (830) TG 103, x-Fold 0.98 Diphenylborinic acid (50 mg) and aspartic acid (25 mg) were stirred with heating in ethanol, water 1:1 mixture (1 mL) at 70 C. for 1 hr to give the title compound (6 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.9% | With sodium hydroxide;lanthanum(III) carbonate; In water; at 91 - 93℃; for 36.0833h;pH 9.53 - 10.21;Product distribution / selectivity; | Example 1 Preparation of a mixture of AES and ISA; 98.06g (1 .000 mole) of maleic anhydride was dissolved in 258.40g of water using a magnetic stirrer and heating to about 70 C. The aqueous maleic acid solution was transferred into a three-neck flask in a preheated oil bath, of La2(C03)3 (0.263 moles) was added to the maleic acid solution. The addition was made slowly dur- ing about 5 minutes for controlling the effervescence caused by carbon dioxide.). 31 .14g (0.252 moles) of diethanol amine was added into the reaction mixture. The temperature of the mixture was raised to about 90 C. The pH of the reaction solution was adjusted by adding 77.61 g (0.931 moles) of NaOH solution (aq. 48 wt%). The alkalinity of the reaction mixture was adjusted in connection with the second sample by adding 4.47g (0.054 moles) of NaOH solution (aq. 48 wt%), whereby the pH raised to 8.55, and in connection with the third sample by adding 7.35g (0.088 moles) of NaOH solution (aq. 48 wt%), whereby the pH i raised to 9.16.After 12 hours from the start of the measurements 61 .71 g (0.459 moles) of DL- aspartic acid was added. The alkalinity was restored by adding 74.00g (0.888 moles) of NaOH solution (aq. 48 wt to pH 9.98 (T = 93 C). After the addition of aspartic acid and NaOH monitoring samples were taken with an interval of half an hour during six hours. The reason for that was the fast synthesis of ISA from aspartic acid and maleate especially in the catalyzed reaction. At each occasion two samples were taken. Into one of the samples warm 30% by weight Na2C03 solution was added immediately to stop the reaction catalyzed by lanthanum at the sampling moment. The other sample was stored and frozen. The analysis was performed on the samples treated with the carbonate solution. During the synthe- sis samples were taken at 23 moments. The total duration of the synthesis was 60 hours of which the 12 first were pure synthesis of AES.More accurate information regarding the conditions and concentrations of the reaction mixture are set forth in following table 1 .Table 1The results in Table 1 show that when asparic acid is added to the reaction mixture, it stats reacting with unreacted maleate present in the reaction mixture, whereas the formation of additional AES is essentially stopped.The results additionally show that after a reaction time of about 24 hours the yield of AES was about 35 mole% and the yield of ISA was about 50 mole% (based on the starting aspartic acid). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
> 95% | With water; In N,N-dimethyl-formamide; at 65℃; for 3h; | 5.22 mg (0.0045 mmol) of aspartic acid (Asp) were dissolved in 8 mL of H20 in a 20mL vial. To the clear solution were added 270 mu^ of Cr( 03) -9H20 solution in DMF. The solution was placed in an isothermal oven of 65C for 3 hrs, which yielded a color change to crimson. The color changed indicated the formation of the Cr(Asp)3. The solvent was allowed to evaporate to form a crimson solid. The solid was collected in a quantitative yield of >95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With sodium carbonate; In tetrahydrofuran; water; for 0.333333h;Cooling with ice; | Aspartate 10.5 g 0.0789 mol 1 EqPhSNPPOC-Cl 30.0 g 0.0789 mol 1 EqNa2C03 23.0 g 0.22 mol 2.8 EqWater 1000 mlTHF 1200 mlThe corresponding synthesis pathway is depicted in Fig. 4i. 10,5g aspartate and 23 g Na2C03 are dissolved in 1000 mL water and 1000 mL THF. The solution is stirred in an ice-bath and is dropwise treated with a solution of 30 g PhS PPOC-Cl in 200 mL THF. Stirring is continued for 20 min. THF was evaporated. The solution is extracted twice with approximately 500 mL hexane/ethylacetate 1 : 1, the pH is adjusted to 2 with dilute HCl and extracted with approximately 500 mL ethylacetate. The organic phase is washed with approximately 500 mL Water and evaporated to dryness. The product is purified by column chromatography on silica gel with methanol in dichlormethane (0 to 2 %).Yield: 28 g pale yellow amorphous foam (74 %) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Ca. 54% | After dissolution of 2 mmol of aspartic acid (0.2662 g) and 2 mmol of guanidoacetic acid (0.2342 g), the solution of guanidoacetic acid was slowly added to the aspartic acid solution under strong stirring at 43 C for three hours. The solution was freezed at 4 C for 1 h and then kept in a sealed glass tube at room temperature for 2 days. Any formed solid was eliminated. When a clear and dense solution was obtained, 2 mmol of Ni(NO3)2 (0.5816 g) were added. The solution was then stirred and heated at 45 C for 3 h. After another 5 h elapsed, a solution of KOH 5 mol/L was slowly added until a pH3O+ = 3.4 was obtained. The glass tube was then sealed and stored for 2 days; at this stage the volume of the solution had been reduced by 50% so the volume was then filled to 100% by adding absolute ethanol. The product was washed with solutions: (a) 60 mL ethanol + 30 mL methanol + 10 mL acetone and (b) 60 mL ethanol + 5 mL HNO3 + 20 mL diethyl ether. The product was then dried in a sealed vessel with CaCl2. Yield around 54%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water;pH 6.0 - 7.0; | Mix 133 g of D-aspartic acid and 133 g of L-aspartic acid in 250 ml of distilled water. Then, under continuous stirring, add 480 ml of NaOH 4 M (4 M = 160g/l) and stir in order to solubilise D-aspartic acid and L-aspartic acid. After solubilisation the pH of the solution will be 6.0-7.0. If the pH value is higher than 7.0, then adjust to pH 6.0-7.0 with few ml of HCl 2M. If on the contrary the pH is lower then 6.0-7.0, then add more NaOH until the pH value is again 6.0-7.0. Then add 0,9 g of potassium sorbate and 0,9 g of sodium benzoate. Finally add distilled water to a final volume of 1 litre. Filter through 0.45 mum pore membranes (millipore) or 3 MM paper in order to separate insoluble residue and at the same time to sterilize the solution. Successively distribute in 10 ml bottles. Finally add in bottle dosing cap 2 mg of vitamin B6, 0,3 mg of folic acid, 1,5 mucg of vitamin B12 and possibly orange aroma or fructose or other excipient in amount to be established depending on drug desired taste. 10 ml of the solution contain 1.56 g of sodium D-aspartate and 1.56 g of sodium L-aspartate (corresponding to 1.33 g of D-aspartic acid and 1.33 g of L-aspartic acid respectively). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; In water; at 90℃; for 11h;Reflux; | Example 5. Preparation of PP-Sulf-Asp and PP-Cres-Asp. These chelating agents were prepared by a base catalyzed (KOH) condensation of their respective para-substituted phenol precursors (p-cresol (Cres), 4-hydroxybenzenesulfonic acid (Sulf), aspartic acid, and 37% aqueous formaldehyde solution (all commercially available). For the synthesis of PP- Sulf- Asp, 1 molar equivalent of aspartic acid, 2 molar equivalents formaldehyde, and 2 molar equivalents KOH were dissolved in a small amount of water and added to an aqueous solution of 1 molar equivalent Sulf. For the synthesis of PP-Cres-Asp, 1 molar equivalent of aspartic acid, 2 molar equivalents formaldehyde, and 2 molar equivalents KOH were dissolved in small amount of water and added to a solution of 1 molar equivalent Cres dissolved in water- methanol (1:2 v/v) solvent. The resulting mixtures were refluxed at 90 C for 11 hr. After 11 of reflux, the solution was cooled to room temperature, and solvent removed by roto-evaporation to yield a solid product. The purity of the PP-Sulf-Asp and PP-Cres-Asp chelating agents were analyzed by 1H- NMR. 1H-NMR of PP-Cres-Asp (Figure 15) (400 MHz, D20): delta (ppm) 2.23 (s, 6H), 3.07 (m, 2H), 4.08 (t, H), 4.28 (dd, 2H), 4.40 (dd, 2H), 6.7 (d, 2H), 7.02 (d, 2H), 7.1 (s, 2H). . 1H-NMR of PP-Sulf-Asp (Figure 14) (400 MHz, D20): delta (ppm) 2.76 (m, 2H), 3.79 (m, H), 3.95 (m, 2H), 4.25 (m, 2H), 6.95 (m, 2H), 7.5 (m, 2H), 7.67 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.1% | With 1H-imidazole; zinc diacetate; In ethanol; at 120℃;Inert atmosphere; | 1.00 g (2.55 mmol) of perylene-3,4,9,10-tetracarboxylic dianhydride, 0.849 g (6.37 mmol) DL-aspartic acid, 0.200 g(0.912 mmol) zinc acetate and 18 g imidazole were heated at 120 C for 6 h under nitrogen atmosphere. Then 50 mL of ethanol was poured into the hot mixture, refluxed for 6 h and kept for overnight to precipitate out. The precipitate was filtered and washed with ethanol. The product was dried at 70 C under vacuum oven to get 1.32 g deep red powder, named as PDIC, with a yield of 83.1%. 1H NMR (D2O, 400 MHz,d ppm): 7.46 and 8.67 (each d, 8H, perylene),5.77 (t, 2H, CH), 2.91-3.35 (m, 4H, CH2). IR (KBr pellet) vmax in cm-1 3141 (perylene C-H stretching vibration), 2959 (DL-aspartic acid aliphatic chain CeH stretching vibration), 2849 (asymmetric CH2 stretching vibration), 1699 (perylene imde C=O), 1657 (peryleneimide C=O), 1592 (perylene C=C), 1353 (C-N), 1260 (carboxylic acid C-O), 1021 (carboxylic acid C-O), 858 (perylene C-H out-of-plane bending), 808 (C-H), 751 (CeH). |
With 1H-imidazole; at 150℃; for 6h;Inert atmosphere; | PASP was prepared by an improved method from the literature. [46,47] Briefly, 3,4,9,10-perylenetetracarboxylic acid bisanhydride (392.8 mg, 1.0 mmol), aspartic acid (273.4 mg, 2.05 mmol), and 5.000 g of imidazole were added into a round bottom flask under mechanical stirring for 6 h under N2 atmosphere at 150 C. The reaction mixture was cooled to 90 C, and then 100.0 mL of water was poured into the reactor. After the insoluble impurities were removed, 250.0 mL of 2.0 M HCl was added to the aqueous solution. The fresh precipitate was washed twice with water and ethanol, and then dried under vacuum at 80 C to give the crude product. The crude product was further purified by dissolving it in 50.0 mL of dimethylformamide (DMF), using 2.0 M HCl to adjust to pH 1, and then the obtained precipitate was dissolved in 50.0 mL of a KOH solution (4.5 mmol, 252.5 mg), and 0.12 M HCl added dropwise to adjust the pH to 1. The final precipitate was washed twice with ethanol and then dried under vacuum at 80 C to give the product of PASPH*2O. | |
With 1H-imidazole;Inert atmosphere; Reflux; | (1) Weigh perylene dianhydride (PTCD, 196.4mg, 0.50mmol), aspartic acid (ASP, 136.7mg, 1mmol), imidazole (2.0g) and 100mL single-necked round bottom flask, stir under N2 protection, Heated to 150-180 , refluxed for 6-10h to obtain a dark red solution. The reaction liquid was cooled to room temperature, the liquid solidified, and 50 mL of hot water was added to the reactor. The product was dissolved in hot water and centrifuged to remove insoluble impurities; the aqueous solution was acidified with HCl (120 mL, 1-2 M) to obtain a red precipitate, centrifuged, and washed with water 2. Wash twice with ethanol to obtain a red precipitate, and vacuum dry at 80 C to obtain a crude red product. Dissolve the crude product in 25mL N,N-dimethylformamide (DMF), dropwise add 1-2M HCl to pH = 1 (the solution is close to colorless, the maximum amount of red precipitate), centrifuge; dissolve the precipitate in KOH aqueous solution In the solution, add 1-2M HCl dropwise to pH = 1, centrifuge, wash with water and wash with ethanol twice, and vacuum dry at 80 . The crude product was repeatedly dissolved with KOH and acidified with 1-2M HCl 2-3 times to obtain the red product PASP. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47.2% | Take 1.2 (^ (9.1111111101) aspartic acid and 1.528 Sodium bicarbonate (18.111111] 101), Dissolved in 101111 ^ deionized water, A 1.5 mL formaldehyde aqueous solution (37%, 18 O mmol) was added, The reaction was stirred at room temperature for 2 hours, The reaction solution was diluted with 50 mL of methanol, 1.1 lg (3. Ommol) of curcumin was added, The reaction was stirred at room temperature for 2 hours, TLC monitoring to curcumin reaction is complete, drop the appropriate amount of 0.5M dilute hydrochloric acid and sodium bicarbonate, the reaction product by silica gel column chromatography separation, dichloromethane / methanol / glacial acetic acid mixed solvent elution, curcumin - aspartic Amino acid conjugate 1.23 g, yield 47.2% (synthetic route shown in Figure 23). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; at 65 - 95℃; for 30h;pH Ca. 9; | Example 4 (0047) Molar ratio of the raw materials is: raw material A (1.0); raw material B (0.9-1.0); alkali metal hydroxide (2.0-3.0); and water (35-40). (0048) To a 2 L four-necked flask pre-charged with water of 550 g (30.6 mol), with stirring on, slowly add in sequence of the following: 32% sodium hydroxide solution of 250 g (including sodium hydroxide 2.0 mol, and water 9.4 mol), fumaric acid sodium salt of 128 g (1.0 mol), D,L-hybrid configuration aspartic acid of 120 g (0.9 mol). In the whole charging process, adjust raw material charging speed and control temperature to no more than 65 C. After all raw materials are added, stir for 5 min until uniform, and at this stage, pH of the mixture is about 9. Then, heat the mixture up to 90±5 C. and maintain at this temperature for 30 hours for the reaction to occur. Once the reaction is finished, cool down to room temperature to receive a mixed solution with a solid of 30%, and 70% of the solid being tetrasodium iminodisuccinic acid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium carbonate; In tetrahydrofuran; water; at 10 - 15℃; for 24h; | To a solution of Na2CO3 (3.18 g, 30 mmol) and aspartic acid (4.12 g, 30 mmol) in water (30 mL) was added 4-methoxycinnamic acid N-hydroxysuccinimide Acid N-hydroxysuccinimide ester (5.50 g, 20 mmol) dissolved in tetrahydrofuran (60 mL) was added thereto while maintaining the temperature at about 10 C. The reaction solution is stirred at 10 to 15 C for 24 hours. The filtrate was concentrated under reduced pressure to remove tetrahydrofuran in the reaction solution, and the remaining water layer was washed twice with ethyl acetate (30 mL). It is acidified to pH 1-2 with concentrated HCl and then stirred for a further 5 hours while maintaining 0-5oC. The resulting precipitate was filtered and recrystallized from ethanol to obtain 3,67 g (78%) of N- (4-methoxycinnamoyl) aspartic acid as a precipitate . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 7. Preparation of compound of formula (VIII) ( ASPHA ) To 940 g (10 mol) of phenol at 40 C, 133 g (1 mol) of aspartic acid was slowly added without leaving the temperature to raise over 45 C. Once the addition was finished, the reaction mixture was allowed to cool down and 80 g (1 mol) of 50% w/w sodium hydroxide aqueous solution was added. After cooling the reaction crude to 35 C, 148 g (1 mol) of 50% w/w glyoxylic acid aqueous solution was slowly and continuously added, keeping the temperature under 40 C during all the reaction. Then, the mixture was allowed to react for 2-4 hours at 70-75 C. Finally, 90 g (5 mol) parts of water were added and the aqueous phase was extracted twice with 1 120 g (10 mol of chlorobenzene. The aqueous phase contained the chelating agent ASPHA. Quelation of Fe-ASPHA was subsequently made directly over the obtained aqueous solution. For the chelation, to the aqueous solution obtained above containing the chelating agent ASPHA, 162.3 g (1 mol) of FeCI3 and 240-320 g (3-4 mol) of 50% w/w sodium hydroxide aqueous solution until obtaining a pH of 8-9 were added. Finally, after removing water by distillation under reduced pressure, the iron chelate in form of dark brown powder/microgranules was obtained. The iron content of the product varied from 8-9 wt.%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 8. Preparation of of compound of formula (IX) ( CREASPHA ) To 1 180 g (10 mol) of p-cresol at 40 C, 133 g (1 mol) of aspartic acid was slowly added without leaving the temperature to raise over 45 C. Once the addition was finished, the reaction mixture was allowed to cool down and 80 (1 mol) of 50% w/w sodium hydroxide aqueous solution was added. After cooling the reaction crude to 35 C, 148 g (1 mol) of 50% w/w glyoxylic acid aqueous solution was slowly and continuously added, keeping the temperature under 40 C during all the reaction. Then, the mixture was allowed to react for 2-4 hours at 70-75 C. Finally, 90 g (5 mol) parts of water were added and the aqueous phase was extracted twice with 1 120 g (10 mol of chlorobenzene. The aqueous phase contained the chelating agent CREASPHA. Quelation of Fe-CREASPHA was subsequently made directly over the obtained aqueous solution. For the chelation, to the aqueous solution obtained above containing the chelating agent CREASPHA, 162.3 g (1 mol) of FeCI3 and 240-320 g ( 3-4 mol) of 50% w/w sodium hydroxide aqueous solution until obtaining a pH of 8- 9 were added. Finally, after removing water by distillation under reduced pressure, the iron chelate in form of dark brown powder/microgranules was obtained. The iron content of the product varied from 8-9 wt.%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; In ethanol; water; at 70 - 80℃; for 144h; | General procedure: A stirred mixture of DL-Aspartic acid (2.5 g, 24.0 mmol),synthon B (Fig. 5) (2.0 g, 6.35 mmol) and sodium hydrogen carbonate(4.5 g, 53.6 mmol) in 50% aqueous ethanol (200 mL) was heatedat 70-80 C for 6 days under reflux conditions. The mixture slowlydeveloped bright yellow, then into clear orange solution. The progressof the reaction was monitored by TLC, and was completedwithin 8 days. The mixture was worked up as described for compound36. The titled compound was collected as bright yellowsolid; 1H NMR (300 MHz, DMSO-d6): d 1.27 (t, J = 7.7, 3H, CH2CH3),2.95 (d, d, d, J = 5.1, 14.7, 10.2 Hz, 2H, CH2-CO2H), 4.10 (m, 2H,CH2CH3), 4.85 (d, d, J = 5.0, 13.5 Hz, 1H, CH-NH), 7.47 (d,J = 8.7 Hz, 1H, NH), 8.14 (d, 3JH-F = 13.6 Hz, 1H, H-5), 8.90 (s, 1H,H-2), 12.51-13.32 (2m, 2H, C-100-COOH and C(3)-COOH), 14.72(brs, 1H, C-200-COOH); 13C NMR (300 MHz, DMSO-d6): d 15.58(CH3), 37.12 (CH2-CO2H), 51.88 (CH2CH3), 54.99 (d, J = 12.07 Hz,CH-NH), 109.8 (C-3), 115.12 (d, 2JC-F = 22.8 Hz, C-5), 118.47 (d,3JC-F = 7.12 Hz, C-4a), 129.35 (d, 3JC-F = 5.17 Hz, C-8), 133.45(C-8a), 137.99 (d, 2JC-F = 14.17 Hz, C-7), 150.67 (d, 1JC-F = 248.7Hz, C-6), 151.08 (C-2), 165.54 (C(3)-CO2H), 172.55 (C-100-CO2H),172.62 (C-200-CO2H), 175.45 (d, 4JC-F = 2.47 Hz, C-4); HRMS (ESI,+ve): m/z [M+] 412.07 C16H15FN3O9 requires: 412.07875. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With ammonium hydroxide; hydrogen; at 219.84℃; under 7500.75 Torr; for 2h;Autoclave; Alkaline conditions; | General procedure: The catalytic transformation of lactic acid andother biomass-derived acids was performed in an autoclave. For example, forthe conversion of lactic acid, the Ru/CNT catalyst and lactic acid were added to the reactor that had been precharged with aqueous ammonia. After theintroduction of H2 at a pressure of 1 MPa, the reactor was placed in a metaljacket wafer on an electronic hotplate (typically 493 K). After a fixed time,the reaction was quickly terminated by cooling the reactor to room temperaturein cold water. The catalytic transformation of glucose to lacticacid was performed in a round-bottom flask with Schlenk line. Degassedwater was added to the reactor that had been precharged with glucose andBa(OH)2 under N2 atmosphere. The flask was put in an oil bath on an electronicstirrer. After a fixed time, the liquid product was neutralized withsulfuric acid and filtered to remove Ba2+. The filtrate was added equal mole ofNaOH to prevent organic acids lose during freeze-dry. After freeze-drying, theproducts were acidified with HCl and used as the substrates in the aminationstep. The liquid products were analyzed by HPLC (Shimazu LC-20A) equippedwith both RI and UV detectors. Glucose and hydroxyl acids were quantifiedon an Agilent Hi-Plex H column (7.7 × 300 mm, 8 mum) using a dilute H2SO4aqueous solution as the mobile phase, whereas amino acids were analyzed ona Poroshell 120 EC-C8 column (4.6 × 100 mm) by using a precolumn derivatizationmethod, where ortho-phthalaldehyde was used as the derivatization reagent.The dehydrogenation of isopropanol (IPA) over Ru and Pd catalysts was performed in a fixed bed flow reactor equipped with an online gaschromatography (GC, Agilent 7890A). A flame ionization detector (FID) andan Agilent Cyclodex-B column (30 m × 250 mum × 0.25 mum) were used todetect and analyze IPA and gas products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With dipotassium peroxodisulfate; silver nitrate; In water; acetonitrile; at 60℃; for 3h; | 10 g (75.1 mmol) of aspartic acid D, L-aspartic acid, 16.4 g (112.7 mmol) of 2-hydroxyquinoline, 1.0 g (6 mmol) of silver nitrate were added to a mixed solution of 400 mL of acetonitrile and 100 mL of water.The temperature was raised to 60 C, and 300 mL of a 0.12 g/mL potassium persulfate aqueous solution was slowly added dropwise, and after the completion of the dropwise addition, the reaction was carried out at 60 C for 3 hours. The reaction solution was cooled to room temperature, 400 mL of purified water was added, and the mixture was extracted with ethyl acetate 800 mL*3, and the organic layer was combined, washed with water (2000 mL*3), dried over anhydrous sodium sulfate, filtered, filtered, 6.1 g (26.3 mmol) of (R,S)-2-amino-3-[2(1H)-quinolone-4]propanoic acid, molar yield: 35% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In water; at 50 - 90℃; for 1h;Sonication; | Add 0.7g of aspartic acid to the 100ml reaction bottle.Add 35ml water, heat to 80-90 ° C, stir for 0.5 hoursTo dissolve clarification,Adding tinofevir levamide 2.35g,Stir for 10-20 minutes until the solution is clear, cool down to 50-60 ° C, and sonicate for 1 hour.Gradient cooling (5-10 ° C / hour) to 20 ± 2 ° C crystallization for 15-20 hours.After suction filtration, the solid was dried under vacuum at 50 ° C to give a white solid, 2.75 g, yield: 89percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.9% | General procedure: Equal molar mass of amino acids and KOH were added into ethanol and stirred at 50 C until theamino acids dissolved. Then, 1.2 equivalent molar mass of cinnamaldehyde was added drop-by-dropover 30 min at room temperature with constant stirring. After addition, the mixtures were constantlystirred and allowed to react for two hours. After reaction, the solvent was evaporated at 35 C untilprecipitate formed. The precipitate was then washed three times to remove the extra cinnamaldehyde,as described in Reference [16]. The washed precipitate was the prepared compound. FTIR, 1H-NMR,13C-NMR, MS, and melting point were then used to determine the structures of the compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.5% | With pyrrole aldehyde; In water; at 37℃; for 24h;pH 8; | The reaction was carried out in a 500 mL shake flask.The reaction system is controlled to 150 mL.Taking the compound of formula VI (4S)-4-methyl-2-oxoadipate (11.44 g, 0.065 mol) and 23 g of aspartic acid as a substrate,Using water as a solvent,75g/L genetically engineered whole cell of transaminase derived from Vibrio fluvialis and 0.1g/L pyrrole aldehyde as catalyst.Adjust the pH of the conversion system to 8,The conversion temperature is 37 C,The speed of the shaker is controlled at 160r/min.The conversion time is 24h.After conversion,Obtaining a compound of formula VIIa conversion solution of (2R,4S)-2-amino-4-methyladipate,purification,The compound of formula VII (2R, 4S)-2-amino-4-methyladipic acid is obtained.(10.97g, 0.062mol),The optical purity was 98.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With sodium carbonate; In water; at 70 - 80℃; for 1h; | General procedure: An aqueous sodium carbonate solution (10 ml,1.2 mmol) was added drop wise to the stirred solution of amino acid (1 mmol). Compound 2 was added (0.3g,1 mmol) to the above mixture, stirred vigorously and the reaction mixture was heated at 70-80 for 1-2 hr. The resulting solution was allowed to cool and the pH was brought to 2.5 by adding hydrochloric acid under stirring. The product was separated by filtration and washed with cold water. The progress and completion of the reaction was monitored by TLC. The analytical parameters were recorded in Table-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | CF3COOCH3 (1.3 eq.) and triethylamine (2.0 eq.) were added to a methanol solution (10 mL) of monoaminosuccinic acid (13 g), and the mixture was stirred at room temperature for 17 hours. 1N aqueous hydrochloric acid was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The solvent was distilled off from the extract, and the crude product was recrystallized to give compound 8 (10 g, 44%). An ammonia methanol solution (4.0 eq.) was added to a methanol solution (10 mL) of compound 8 (10 g), and the mixture was stirred at room temperature for 1 hour. Thereafter, the solvent was distilled off to give compound 9 (12 g, quant.). |
[ 323194-76-9 ]
Sodium (S)-3-amino-3-carboxypropanoate hydrate
Similarity: 0.97
[ 215533-00-9 ]
Magnesium L-aspartate dihydrate
Similarity: 0.97
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :