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CAS No. : | 21085-72-3 | MDL No. : | MFCD00061613 |
Formula : | C13H17BrO9 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 397.17 | Pubchem ID : | - |
Synonyms : |
|
Chemical Name : | (2R,3R,4S,5S,6S)-2-Bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate |
Num. heavy atoms : | 23 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.69 |
Num. rotatable bonds : | 8 |
Num. H-bond acceptors : | 9.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 76.59 |
TPSA : | 114.43 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) : | -8.3 cm/s |
Log Po/w (iLOGP) : | 2.37 |
Log Po/w (XLOGP3) : | 0.6 |
Log Po/w (WLOGP) : | 0.07 |
Log Po/w (MLOGP) : | -0.17 |
Log Po/w (SILICOS-IT) : | 0.26 |
Consensus Log Po/w : | 0.63 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.15 |
Solubility : | 2.8 mg/ml ; 0.00704 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.58 |
Solubility : | 1.05 mg/ml ; 0.00265 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -0.94 |
Solubility : | 45.7 mg/ml ; 0.115 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 4.82 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | 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 |
---|---|---|
With methanol Behandeln des Reaktionsprodukts mit Acetanhydrid und Pyridin; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.98% | With hydrogen bromide; acetic acid; at 0 - 20℃; for 2h; | Compound 8 (5 g, 0.0133 mol) was slowly added to 33 % acetic acid solution of hydrogen bromide (20 mL) at 0 C. The mixture was stirred at room temperature for 2 h. Benzene (50 mL) was added to the mixture, and the resulting mixture was concentrated under reduced pressure to syrup. The syrup was dissolved with ethyl acetate (100 mL). Then the mixture was washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford 9 (5.12 g, 96.98%). mp 102.5~103.8 C; ESI-MS (m/z): Cacld for [C13H18BrO9]+} 397.0134/399.0114, found 396.9410/398.9388. 1H NMR(300 MHz, CDCl3) delta: 5.79, 5.77 (1H, d, -CH), 5.34~5.13 (3H, m, 4×-CH), 4.21, 4.18 (1H, d, -CH), 3.75 (3H, s, -OCH3), 2.05~2.04 (9H, m, 3×-COCH3); 13C NMR (75 MHz, CDCl3) delta: 169.80, 169.03, 168.45, 167.88 (4×-COCH3), 89.16 (-CH), 72.95, 71.42, 70.22, 69.89 (4×-CH), 52.79 (-OCH3), 20.45, 20.41, 20.38 (3×-COCH3). |
95% | With titanium(IV) bromide; In dichloromethane; at 20℃; for 8h;Cooling with ice; | To an ice-cold solution of 1,2,3,4-tetra-O-acetyl-13-D-glucuronide methyl ester (50g, 132.80 mmol) in DCM (600 mL) was added titanium bromide (50.20 g, 136.80 mmol).The reaction mixture was left to warm to room temperature and stirred at this temperature for 8 h. After the reaction was deemed complete by TLC monitoring, the solution was diluted with ice-cold water (500 mL) and the organic layer was extracted with DCM (2 x 500 mL). The combined organic extracts were dried over sodium sulfate, filtered andconcentrated under reduced pressure to afford the title compound (50 g, 95%) as a pale- yellow solid that was used without further purification. |
95% | With titanium bromide; In dichloromethane; at 20℃; for 8h;Cooling with ice; | Example 1 Preparation of (2R,3R,4S,5S,6S)-2-Bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl Triacetate To an ice-cold solution of 1,2,3,4-tetra-O-acetyl-beta-D-gluocuronide methyl ester (50 g, 132.80 mmol) in DCM (600 mL) was added titanium bromide (50.20 g, 136.80 mmol). The resulting mixture was allowed to warm to room temperature and stirring was continued for 8 h (reaction complete by TLC monitoring). The reaction mixture was then diluted with ice-cold water (500 mL) and the organic layer was extracted with DCM (2*500 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the title compound (50 g, 95%) as a pale-yellow solid that was used without further purification. |
92% | With sulfuric acid; sodium bromide; In tert-butyl methyl ether; at 45 - 50℃; for 24h; | (1) Add 1000g to 10L MTBE solvent while stirring bBeta-tetra-O-acetylglucuronic acid methyl ester,After the system was stirred and dissolved, 273 g of sodium bromide was added. After the feeding, the system was heated to 45 C.Then, 266 g of concentrated sulfuric acid was added dropwise to the system with stirring,Control the temperature of the system in the range of 40 C to 50 C during the dropping process;After the dropwise addition, the system is kept at 45 ± 5 for reaction,HPLC tracks the reaction,The material disappears after about 24 hours,After the reaction is completed, the bodyThe temperature was lowered to 25 , and the system was filtered to obtain sodium sulfate crystals; (2) The filtrate obtained in step (1) is concentrated to about 3 L at normal pressure,Collect the distilled methyl tertiary ether and continue to use in the next batch of reactions.Then the temperature was lowered to 0 C with stirring for 3 hours, and the product and mother liquor were obtained after filtration;The mother liquor can be directly used in the next batch of reactions without concentration.Product alpha-tri-O-acetyl methyl glucuronide bromide,After drying, the mass was 971 g, the yield was 92%, and the purity was 99.5% by HPLC. |
90% | With hydrogen bromide; acetic acid; at 10 - 20℃; for 2h; | Add 1,2,3,4-tetra-O-acetyl-D-glucuronic acid methyl ester (3) (15.0 g, 4 mmol) to a solution of hydrogen bromide in acetic acid (% by mass of hydrogen bromide) 33%) (60 mL) remained stable no more than 10 C, then naturally warmed to room temperature and stirred for 2 hours. The reaction was concentrated to dryness and then purified with ethyl acetate ethyl acetate. The solid was filtered to give acetobromo-alpha-D-glucuronic acid methyl ester(4) (yield: 14.3 g, yield: 90%). |
89% | With bromine; In ethyl acetate; at 30℃; for 19h;Irradiation; Green chemistry; | General procedure: Bromine (1.5 mmol, 0.08 mL) was added slowly to a magnetic stirring barand perfluorohexanes (4.0 mL) in a test tube (14 mmphi x 105 mm) with a septum and then 1-O-acetylsugar 1a (1 mmol, 392 mg) in ethyl acetate (2.0 mL) wasadded slowly, forming three layers. The test tube was stirring upon irradiationwith 15 W black light (at 352 nm, TOSHIBA EFD15BLB-T) at 30 C. The light source wasplaced away from the test tube. After 23 hours, the bromine layer disappearedand the fluorous layer recovered transparency. The ethyl acetate layer wastaken up with a pipette. Then, additional ethyl acetate (2 mL x 4) was placedon the residual FC-72 layer, followed by decanting off. The combined ethylacetate layer was washed with water (15 mL), aqueous sat. NaHCO3 (20mL), brine (20 mL) and, dried over Na2SO4, andconcentrated. Purification by chromatography on silica gel with hexane/AcOEt = 2/1gave glycosyl bromide 2a (0.91 mmol,374 mg) in 91% yield |
83.9% | With hydrogen bromide; acetic acid; In dichloromethane; at 0℃; for 2h;Inert atmosphere; | 25.6 g of methyl 1,2,3,4-tetra-O-acetyl-beta-D-glucuronide (4) (68.0 mmol) was dissolved in 120 ml of dichloromethane under nitrogen and cooled to At 0 C, 150 mL of 33% HBr in acetic acid was added dropwise. Stirring was continued for 2 hours at this temperature. TLC was applied. After completion, it was diluted with water and extracted with dichloromethane. The organic layer was washed with saturated sodium hydrogen carbonate and brine. The aqueous solution was dried over sodium sulfate, filtered, evaporated, evaporated22.7 g of a white solid were obtained in a yield of 83.9%. |
82% | With hydrogen bromide; acetic acid; In dichloromethane; at 0 - 20℃; for 0.666667h; | (2S,3R,4S,5S,6S)-6-(methoxycarbonyl)tetrahydro-2H-pyran-2, 3,4,5- tetrayl tetraacetate 18 (2.0 g, 5.31 mmol) was dissolved in CH2CI2 (20 mL) and cooled to 0 C. To this solution was added a solution of 33% HBr in AcOH (10 mL) dropwise over 10 minutes. The mixture was stirred at 0 C for 30 minutes and then allowed to warm to room temperature. The reaction mixture was diluted with CH2CI2 and washed with sodium bicarbonate solution, followed by brine. The organic layer was dried over MgS04, filtered and evaporated to give an orange syrup. Toluene was added and the residue evaporated to dryness three more times. The same azeotroping process was repeated with ether to give a light beige solid in 1.75 g for a 82% yield. |
14% | With hydrogen bromide; In dichloromethane; water; at 20℃; for 4h;Cooling with ice; | Methyl-1,2,3,4-tetra-O-acetyl-beta-D-glucuronate (1.5 g, 4.50 mmol) was dissolved in 20 mL of DCM, and hydrogen bromide (2.34 mL, 3.0 eq.) was added thereto in an ice bath. After the dropwise addition, the ice bath was removed, and the mixture was stirred at room temperature for 4 hours. After the completion of reaction, H2O was added, and the mixture was subjected to extraction with CHCl3. The organic layer was washed with brine, dried by adding anhydrous sodium sulfate, and then distilled under reduced pressure. Then, the residue was purified by column chromatography (hexane:EtOAc=4:1) to isolate and obtain a compound 45 (0.22 g, 14%) as a white crystal. |
With hydrogen bromide; In acetic acid; for 3.5h; | Methyl yl (2,3,4-tri-O-acetyl-ss-D-glucopyranosyl azide) uronate (2) Methyl (2,3, 4-tri-O-acetyl- (3-D-glucopyranosyl azide) uronate was prepared by reference to the methodology of Tropper, F. D. et al., Synthesis, 1992,618-620. Methyl 1, 2,3, 4-tetra-O-acetyl- P-D-glucopyranuronate (Bollenback, G. N. et al. J. Am. Chem. Soc., 1955,77, 3310-3315) (1.23 g, 3.26 mmol) was dissolved in HBr/AcOH solution (20 mL, 33% HBr in AcOH) and the solution was stirred. After 3.5 hours the mixture was diluted with CH2Cl2 (100 mL), washed with ice-cold water (2 x 100 mL), saturated sodium bicarbonate (3 x 100 mL), and brine (100 mL). The organic layer was dried (MgS04), filtered and the filtrate evaporated in vacuo to afford a pale yellow oil. This oil was dissolved in CH2CI2 (50 mL), and saturated sodium bicarbonate solution (50 mL), sodium azide (1.1 g, 17 mmol) and tetrabutylammonium hydrogensulfate (1. 1 g, 3.2 mmol) were added. The mixture was stirred vigorously for 16 hours and then CH2Cl2 (150 mL) was added and the solution was washed with saturated sodium bicarbonate (3 x 200 mL), brine (1 x 100 mL), then dried (MgS04), filtered and the solvent evaporated in vacuo to afford Methyl (2,3, 4-tri-O-acetyl-p- D-glucopyranosyl azide) uronate as a white crystalline solid (1.00 g, 85%), m. p. 135-137 C [lit. m. p. 153 C (Gyorgydeak, Z. and Thiem, J. Carb. Res., 1995, 268, 85-92)].'H NMR (500 MHz, CDCl3) 6 5.23 (t, 1H, J= 9.1 Hz, H3); 5. 18 (t, 1H, J= 9.5 Hz, H4); 4.91 (t, 1H, J= 8.8 Hz, H2); 4.68 (d, 1H, J = 8.7 Hz, H1) ; 4.09 (d, 1H, J = 9.6 Hz, H5) ; 3.73 (s, 3H, COOCH3) ; 2.03 (s, 3H, COCH3) ; 1.98 (s, 3H, COCH3) ; 1.97 (s, 3H, COCH3). 13C NMR (125 MHz, CDCl3) 8 169.9 (C=O), 169.2 (C=O), 169.0 (C=O), 166.5 (C=O), 88.0 (Cl), 74.2 (C5), 71.8 (C3), 70.4 (C2), 69.0 (C4), 53. 0 (COOCH3), 20.4 (COCH3), 20.34 (COCH3). | |
With titanium(IV) bromide; In dichloromethane; at 20℃; for 24h; | Methyl l-broino-l-deoxy-2,3,4-tri-0- cetyl-o.-D- glucopyr nuronate, compound 10, scheme I.[0045] A solution of 9 ( 1 g, 2.66 mmol) and TiBr4 ( 1 g, 2.72 mmol) in CH2CI2 (30 ml) was stirred at room temperature for 24 h. The mixture was washed with ice water (30 ml) and saturated aqueous NaHCC>3 solution (30 ml), dried over Na2S04, and evaporated to dryness to give 10 (0.95 g, 90%), which was used directly in the next step without further purification. | |
15 g | With hydrogen bromide; acetic acid;Cooling; | Methyl tetra-O-acetyl-beta-D-glucopyranuronate produced according to Example 5, 20 g, is dissolved into 80 mL of 30% hydrogen bromide in acetic acid. The mixture, after solution, is refrigerated overnight. Chloroform, 75 mL, is added to the solution and with moderate stirring a saturated solution of sodium bicarbonate in water is slowly added until the acid wad neutralized. The chloroform is then extracted and dried with sodium sulfate. The chloroform is then removed by rotary evaporation. Absolute ethanol, 65 mL, is then added to the remaining syrup from which crystals began to separate. The mixture is allowed to stand in the refrigerator overnight. Colorless crystals of methyl 2,3,4-tri-O-acetyl-1-bromo-1-deoxy-alpha glucopyranuronate are obtained in a yield of 15 g. The reaction is shown below in Formula (6). |
With hydrogen bromide; acetic anhydride; acetic acid; In dichloromethane; at 0℃; | General procedure: The per-acetylated sugar (1 mmol) was dissolved in DCM (1 mL),acetic anhydride (0.1 mL) and HBr/AcOH (0.8 mL, 30% w/w), and stirred overnight at 0 C. The reaction mixture was diluted with DCM (10 mL), washed with cold water (2 × 5 mL), cold NaHCO3 (2 × 5 mL) and cold brine (5 mL), and dried over MgSO4. After evaporation, thealpha-D-glycosyl bromide was obtained | |
With hydrogen bromide; acetic acid; In dichloromethane; for 2h;Cooling with ice; | Under ice-bath was added dropwise to the above methylene chloride solution of hydrogen bromide in acetic acid solution 70mL, reaction 2h, water was added 200mL stirred 20min, extracted three times with methylene chloride, the organic layer was washed with water three times, saturated sodium bicarbonate adjusted to pH to 7, washed twice with saturated brine, dried over anhydrous sodium sulfate 8h.Column chromatography (petroleum ether: ethyl acetate = 5: 1) to give the intermediate 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.4% | With silver carbonate; In toluene; at 20 - 75℃; for 21.0h;Inert atmosphere; | General procedure: To a stirred solution of methyl (2,3,4-tri-O-acetyl-alpha-d-glucopyranosyl)uronate bromide (3) in dry toluene under Argon atmosphere the corresponding dried alcohol was added and the solution was warmed to 75 C. Subsequently, silver carbonate was added in three portions over a period of 3 h. Then the reaction was stirred at room temperature for 18 h. Afterwards, the suspension was filtered and the filtrate was evaporated to dryness. Purification by flash chromatography (silica gel, cyclohexane-ethyl acetate 1:1) or recrystallisation from i-propanol gave the product 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | In toluene for 3.5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With silver(l) oxide In acetonitrile for 4h; Ambient temperature; | |
66% | With silver(l) oxide In acetonitrile at 0℃; for 4h; Darkness; | |
65% | With silver(l) oxide In acetonitrile at 20℃; |
60% | With silver(l) oxide In acetonitrile at 0 - 20℃; for 16h; Cooling with ice; | 10-1 Step 10-1 - Preparation of (2S,3R,4S,5S,6S)-2-(2-Formyl-4-nitrophenoxy)-6- (methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl Triacetate To an ice-cold solution of 2-hydroxy-5-nitrobenzaldehyde (4.40 g, 26.44 mmol) in100 mL of ACN was added silver(I) oxide (8.80 g, 37.77 mmol), followed by addition of(2R,3R,4S,5S,65)-2-bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate(15.0 g, 37.77 mmol) at 0 °C. The reaction mixture was stirred at room temperature for16 h. After completion of reaction (as determined by TLC), the mixture was filteredthrough diatomaceous earth and the solvent was evaporated under reduced pressure to afford the crude product as dark brown solid. The crude residue was purified by column chromatography (100-200 mesh, 30% EtOAc:Hexane) to afford title compound (11.0 g, 60%) as off-white solid. |
60% | With silver(l) oxide In acetonitrile at 0 - 20℃; for 16h; | 29.29-1 Step 29-1-Preparation of (2S,3R,4S,5S,6S)-2-(2-Formyl-4-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl Triacetate Step 29-1-Preparation of (2S,3R,4S,5S,6S)-2-(2-Formyl-4-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl Triacetate To an ice-cold solution of 2-hydroxy-5-nitrobenzaldehyde (4.40 g, 26.44 mmol) in 100 mL of ACN was added silver(I) oxide (8.80 g, 37.77 mmol), followed by addition of (2R,3R,4S,5S,6S)-2-bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (15.0 g, 37.77 mmol) at 0° C. The reaction mixture was stirred at room temperature for 16 h. After completion of reaction (as determined by TLC), the mixture was filtered through diatomaceous earth and the solvent was evaporated under reduced pressure to afford the crude product as dark brown solid. The crude residue was purified by column chromatography (100-200 mesh, 30% EtOAc:Hexane) to afford title compound (11.0 g, 60%) as off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 96 percent / Ag2O / acetonitrile / 4 h 2: 96 percent / NaBH4; silica gel; isopropanol / CHCl3 / 0.75 h / 0 °C | ||
Multi-step reaction with 2 steps 1: 89 percent / silver oxide / acetonitrile / 4 h / Ambient temperature 2: 99 percent / NaBH4, silica gel HL60 / CHCl3; propan-2-ol / 0.75 h / 0 °C | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 4 h / 20 °C 2: mesoporous silica; sodium tetrahydridoborate / isopropanol; chloroform / 1 h / 0 °C |
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / Inert atmosphere 2: sodium tetrahydridoborate; mesoporous silica / chloroform; isopropanol / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 4 h / 20 °C 2: sodium tetrahydridoborate; mesoporous silica / chloroform; isopropanol / 0.75 h / 0 °C | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 4 h / 20 °C 2: sodium tetrahydridoborate; mesoporous silica / chloroform; isopropanol / 0.75 h / 0 °C | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 18 h / Darkness 2: isopropanol; sodium tetrahydridoborate / dichloromethane / 0 - 5 °C | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 4 h / 20 °C 2: sodium tetrahydridoborate / chloroform; isopropanol / 0.75 h / 0 °C | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 20 °C / Molecular sieve; Darkness 2: sodium tetrahydridoborate; mesoporous silica / chloroform; isopropanol | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 18 h / Darkness 2: sodium tetrahydridoborate / dichloromethane; isopropanol / 1 h / 0 - 5 °C | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 6 h / 0 - 20 °C 2: sodium tetrahydridoborate; triethylamine; mesoporous silica; isopropanol / chloroform / 2 h / 0 °C | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 4 h / 20 °C 2: sodium tetrahydridoborate; mesoporous silica / chloroform; isopropanol / 0.75 h / 0 °C | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 12 h / 20 °C / Schlenk technique; Inert atmosphere; Molecular sieve; Darkness 2: sodium tetrahydridoborate; mesoporous silica / chloroform; isopropanol / 0 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / Darkness 2: sodium tetrahydridoborate / dichloromethane / 1.17 h / 0 °C | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 4 h / 20 °C / Darkness; Inert atmosphere 2: mesoporous silica; sodium tetrahydridoborate / chloroform; isopropanol / 0.75 h / 0 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 20 °C / Inert atmosphere 2: sodium tetrahydridoborate / methanol / 2 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 5 h / 25 - 30 °C / Darkness 2: mesoporous silica; sodium tetrahydridoborate; isopropanol / dichloromethane / 2 h / 0 °C | ||
Multi-step reaction with 2 steps 1.1: sodium hydroxide; benzyl-triethyl-ammonium chloride / chloroform / 16 h / 20 °C 2.1: mesoporous silica / dichloromethane; isopropanol / 0.5 h / 0 °C 2.2: 1 h / 0 °C | ||
Multi-step reaction with 2 steps 1: silver(I) oxide / acetonitrile / 16 h / 20 °C 2: isopropanol; mesoporous silica; sodium tetrahydridoborate / chloroform / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: mercury (II)-cyanide 2: sodium methylate; methanol 3: barium hydroxide; water | ||
Multi-step reaction with 2 steps 1: mercury (II)-cyanide 2: barium hydroxide; water | ||
Multi-step reaction with 3 steps 1: mercury (II)-cyanide 2: sodium methylate; methanol 3: barium hydroxide; water |
Multi-step reaction with 2 steps 1: ethanol 2: barium methylate; methanol | ||
Multi-step reaction with 2 steps 1: benzene; silver carbonate 2: barium methylate; methanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With caesium carbonate In acetonitrile at 70℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tetrabutylammomium bromide; sodium carbonate In ethyl acetate at 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With silver carbonate; In toluene; at 20 - 75℃; for 21.0h;Inert atmosphere; | General procedure: To a stirred solution of methyl (2,3,4-tri-O-acetyl-alpha-d-glucopyranosyl)uronate bromide (3) in dry toluene under Argon atmosphere the corresponding dried alcohol was added and the solution was warmed to 75 C. Subsequently, silver carbonate was added in three portions over a period of 3 h. Then the reaction was stirred at room temperature for 18 h. Afterwards, the suspension was filtered and the filtrate was evaporated to dryness. Purification by flash chromatography (silica gel, cyclohexane-ethyl acetate 1:1) or recrystallisation from i-propanol gave the product 4. |
65% | With silver(l) oxide; In acetonitrile; at 20℃; for 12.0h;Darkness; | To a solution of bromide 4 (1.00 g, 2.52 mmol) in CH3CN (10 mL) is added Ag20 (0.92g, 4.00 mmol) and stirred for 12 h at room temperature in dark. The reaction mixture is filteredthrough short bed of celite washed with CH2C12 (100 mL) and concentrated on reduced pressure. The crude is purified by column chromatography (eluent: EtOAC/hexane; 1:1) to obtain 5 (0.59 g; 65%) as a white solid. ?HNMR (400 MHz, CDC13) 6 5.06-5.16 (m, 2H), 4.87 (t, J 8.0, 111), 4.49 (d, Jr 8.0 Hz, 111), 3.97 (d, Jr 8.0 Hz, 111), 3.77-3.86 (m, 111), 3.64 (s, 3H), 3.40-3.50 (m,111), 1.93 (s, 3H), 1.91 (s, 3H), 1.90 (s, 3H), 1.08 (t, Jr 6.8 Hz, 3H); ?3C NIVIR (101 MHz, CDC13) 6 169.9, 169.2, 169.1, 167.2, 100.3, 72.4, 72.0,71.2, 69.4, 65.6, 52.7, 20.4, 20.3, 14.8 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22.4% | Powdered molecular sieves ( .18 g, 4 A) were heated at l 10C in a 50 ml roundbottom flask fitted with a magnetic stir bar overnight flushed with argon, and allowed to coolto room temperature. 900 mg (2.1 9 mmol) aceto-bromo-f/-D-glucuronic acid methyl ester and748.5 mg (2.64 mmol, 1.2 eq) 2-(Fmoc-amino)ethanol were added under argon, followed by28 ml dichlorometbane. The suspension was stirred tbr 15 minutes at room temperature and then cooled on an ice/NaC I-slurry for 30 minutes. A white precipitate formed during the cooling process. 6763 mg (2.63 mmol, 1.2 eq) silver trilluoromethanesuifonate (AgOTI) was added in 3 portions over a period of--S minutes. After 20 minutes the ice-bath was removed.The previously noted white precipitate started dissolving, while at the same time a grey precipitate started to Form, The reaction was stirred overnight at room temperature and then quenched by addition of 190 1iL triethylamine (2.63 mmol, 1.2 eq). After filtration through a thin Celite 52 1 pad (-0. 1-0,2 cm deep), and subsequent washing ot the Filter cake with 20 ml dichloromethane, the combined filtrates were diluted with dichioromethane to 150 ml. Theorganic phase was washed with 5% NaHCO3 (1 x50 mL) and water (1 xSO mL), then dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo on a rotary evaporator (S 40C water bath) to dryness and then re-dissolved in 2 ml. dichloromethane, The solution was injected onto a VersaPak silica gel flash column (23x1 10mm, 23 g) and the product eluted with 50% ethyl acetate in hexanes. The product-containing fractions wereidentified by TLC (ethyl acetate:hexanes, 1:1), and concentrated in i?acno on a rotary evaporator (S 40 C water bath) to dryness, Trituration ol?the obtained residue with --10 mL diethyl ether yielded the title material as a white crystalline foam. Yield: 293 mg (0,49 mmol, 22.4%), |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester With silver(l) oxide In acetonitrile at 20℃; for 0.0833333h; Stage #2: 4-bromo-2-nitrophenol In acetonitrile at 20℃; for 4h; | 2.4.2 2.4.2. (2S,3R,4S,5S,6S)-2-(4-bromo-2-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (2R,3R,4S,5S,6S)-2-Bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (5 g) wasdissolved in acetonitrile (100 mL). Ag2O (2.92 g) was added to the solution and the reaction was stirred for 5minutes at room temperature. 4-Bromo-2-nitrophenol (2.74 g) was added and the reaction mixture was stirredat room temperature for 4 hours. The silver salt residue was filtered through diatomaceous earth and thefiltrate was concentrated under reduced pressure. The residue was purified by silica gel chromatographyeluting with a gradient of 10-70% ethyl acetate in heptanes to provide the title compound. MS (ESI+) m/z550.9 (M+NH4)+. | |
With silver(l) oxide In acetonitrile at 20℃; for 4h; | 2.2.44.2.44.2 2.44.2. (2S,3R,4S,5S,6S)-2-(4-bromo-2-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate [000933] (2R,3R,4S,5S,6S)-2-Bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (5 g) was dissolved in acetonitrile (100 mL). Ag20 (2.92 g) was added to the solution, and the reaction was stirred for 5 minutes at room temperature. 4-Bromo-2-nitrophenol (2.74 g) was added, and the reaction mixture was stirred at room temperature for 4 hours. The silver salt residue was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with a gradient of 10-70% ethyl acetate in heptanes, to give the title compound. MS (ESI+) m/z 550.9 (M+NH4)+. | |
Stage #1: 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester With silver(l) oxide In acetonitrile at 20℃; for 0.0833333h; Stage #2: 4-bromo-2-nitrophenol In acetonitrile at 20℃; for 4h; | 2.44.2 2.44.2 (2S,3R,4S,5S,6S)-2-(4-bromo-2-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (2R,3R,4S,5S,6S)-2-Bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (5 g) was dissolved in acetonitrile (100 mL). Ag2O (2.92 g) was added to the solution, and the reaction was stirred for 5 minutes at room temperature. 4-Bromo-2-nitrophenol (2.74 g) was added, and the reaction mixture was stirred at room temperature for 4 hours. The silver salt residue was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with a gradient of 10-70% ethyl acetate in heptanes, to give the title compound. MS (ESI+) m/z 550.9 (M+NH4)+. |
Stage #1: 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester With silver(l) oxide In acetonitrile at 20℃; for 0.0833333h; Stage #2: 4-bromo-2-nitrophenol In acetonitrile at 20℃; for 4h; | 2.22.2 2.22.2. (2S,3R,4S,5S,6S)-2-(4-bromo-2-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (2R,3R,4S,5S,6S)-2-Bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (5 g) was dissolved in acetonitrile (100 mL). Ag2O (2.92 g) was added to the solution, and the reaction was stirred for 5 minutes at room temperature. 4-Bromo-2-nitrophenol (2.74 g) was added, and the reaction mixture was stirred at room temperature for 4 hours. The silver salt residue was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with a gradient of 10-70% ethyl acetate in heptanes, to give the title compound. MS (ESI+) m/z 550.9 (M+NH4)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of compound (2) (10 g, 25.72 mmol) in anhydrous toluene (300 ml) were added cadmium carbonate (2.6 g, 15.12 mmol), and the whole was refluxed with a dean stark trap for 12 hours. After cooling methyl ct-acetobromoglucuronate III(10.3 g, 25.94 mmol) was added, and the whole was further refluxed for 24 hours. The precipitate was removed by filtration and washed with mixture of CH2C12/CH3OH: 95/05. The filtrate and washings were combined and evaporated down. The oily residue was purified on Column chromatography on silica gel, eluting with CH2C12/MeOH: 98/02 to gave the protected Glucuronide compound (4) (3.5 g, 5.35 mmol) as a white foam.1H NMR (400 MHz, CDC13): 7.82 (d, J = 9.2 Hz, 1H); 7.75 (dd, Ji = 7.53 Hz,J2 = 1.18 Hz, 1H); 7.56 (dd, Ji = 8 Hz, J2 = 1.18 Hz, 1H); 7.39 (d, J = 8.43 Hz, 2H); 7.33(d, J = 8.43 Hz, 2H); 6.82 (d, J = 8.1 Hz, 1H); 6.50 (d, J = 8.65 Hz,1H); 5.47 (t, J = 9.44Hz, 1H); 5.18 (t, J = 9.44 Hz, 1H); 4.86 (m, 1H); 4.35 (d, J=10.20 Hz, 1H); 3.71 (s, 3 H,CO2Me); 2.05, 1.95, 1.94 (3 s, 9 H, 3 OAc). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To commercially available <strong>[32449-92-6]D-glucurono-6,3-lactone</strong> compound (6) (48.6276 mmol), was added anhydrous methanol (500 mL) and Na metal (200 mg) at 0C. Themixture was stirred under N2 for 5 h. The solution was treated with Amberlite IR- 120(Ir) resin until pH 3. After filtration the solvent was removed in vacuo to give a yellow gum. The residue was partially dissolved in Ac20 (100 mL), and a solution of HC1O4 (0.1 mL) in Ac20 (1 mL) was added dropwise to the reaction mixture at such a rate that the solution did not exceed 40C. The reaction mixture was then stirred overnight at rtunder N2. The product was then dissolved in ethyl acetate, washed with 1 N HC1, H20, and brine, the organic phase was dried over Na2SO4.The solvent was removed in vacuo to afford per-O-acetate intermediate compound (5) (96.5 g, 93%) as a white gum with an ct/f3 ratio of 75:25. The spectroscopic data was consistent with previously reported spectroscopic data (1); Toper-O-acetate compound (5) obtained above (7.73 g, 20.54 mmol) under N2at 0C was added 45% HBr in acetic acid (25 mL) dropwise. The round bottom flask wasplaced inside a desiccator and stirred at 4 C for 48 h. The mixture was diluted with ethyl acetate (100 mL), poured onto ice (50 g). The solution was washed with sat. aq. NaHCO3 (50 mL), brine (50 mL), H20 (100 mL), the organic phase was dried over Na2SO4? filtered, and the solvent was removed in vacuo. The product was purified by flash chromatography(2:1 hexanes/ethyl acetate) to afford the glucuronosyl bromide compound (3) (3.50 g,43%) as a pink gum. The 1H and 13C NMR spectra were consistent with literature data(Bollenback, G.N., Long, J.W., Benjamin, D.G., Lindquist, J.A., J. Am. Chem. Soc., 1955,77, 3310).1H NMR (400 MHz, CDC13):6.64 (d, J = 4.1 Hz, 1H); 5.62 (dd, Ji= 9.9, J2 =9.9 Hz, 1H); 5.25 (dd, Ji = 10.2, J2 = 9.9 Hz, 1H); 4.86 (dd, Ji = 9.9, J2 = 4.1 Hz, 1 H);4.59 (d, J = 10.2 Hz, 1H); 3.77 (s, 3 H, CO2Me); 2.11, 2.06, 2.05 (3 s, 9 H, 3 OAc). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.37% | With silver(l) oxide; In acetonitrile; at 0 - 10℃; for 20h; | To a solution of (2S,3S,4S,5R,6R)-methyl-3,4,5-triacetoxy-6-bromo-tetrahydro- 2H-pyran-2-carboxylate (9.5 g,23.92 mmoles) in acetonitrile (200 mL) is added (0223) <strong>[41833-13-0]4-(hydroxymethyl)-2-nitrophenol</strong> (4 g, 23.65 mmoles). The mixture is cooled to 0 C while stirring. Silver oxide (27.3 g, 117.81 mmoles) is added slowly to the reaction. The mixture is held at 10 C with stirring for 20 hr. The material is filtered and washed with ethyl acetate (200 ml). The material is concentrated under vacuum. The crude product is purified by flash chromatography on silica (EA:PE=5: 1) to give (2S,3S,4S,5R,6S)-methyl 3,4,5-triacetoxy-6-(4-(hydroxymethyl)-2-nitrophenoxy)-tetrahydro-2H-pyran-2- carboxylate (9.80 g, 85.37% yield) as a yellow solid. MS m/z 508 (M+Na). |
40% | With silver(l) oxide; In acetonitrile; at 20℃; for 14h;Molecular sieve; Inert atmosphere; | Preparation of Compound 50e Compound 50d (937 mg, 5.54 mmol) was dissolved in MeCN (15 mL) at room temperature under nitrogen, and compound M (2.0 g, 5.04 mmol), silver oxide (4.66 g, 20.1 mmol), and 4 A molecular sieve (2.0 g) were added thereto, and stirred at room temperature for 14 hours. After the reaction was completed, the mixture was celite-filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was subjected to column chromatography to produce the compound 50e (1.0 g, 40 %). 1H-NMR (600 MHz, CDC13) delta 7.81 (d, J= 1.8 Hz, 1H), 7.54 (dd, J= 1.8, 6.6 Hz, 1H), 7.37 (d, J= 8.4 Hz, 1H), 5.37-5.27 (m, 3H), 5.20 (d, J= 6.6 Hz, 1H), 4.72 (d, J= 6.0 Hz, 2H), 4.21 (d, J= 9.0 Hz, 1H), 3.75 (s, 3H), 2.12 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.04-2.02 (m, 1H). |
40% | With silver(l) oxide; In acetonitrile; at 20℃; for 14h;Inert atmosphere; Molecular sieve; | Compound 50d (937 mg, 5.54 mmol) was dissolved in MeCN (15 mL) at room temperature under nitrogen, and compound M (2.0 g, 5.04 mmol), silver oxide (4.66 g, 20.1 mmol), and 4 A molecular sieve (2.0 g) were added thereto, and stirred at room temperature for 14 hours. After the reaction was completed, the mixture was celite-filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was subjected to column chromatography to produce the compound 50e (1.0 g, 40 %). 1H-NMR (600 MHz, CDC13) delta 7.81 (d, J= 1.8 Hz, 1H), 7.54 (dd, J= 1.8, 6.6 Hz, 1H), 7.37 (d, J= 8.4 Hz, 1H), 5.37-5.27 (m, 3H), 5.20 (d, J= 6.6 Hz, 1H), 4.72 (d, J= 6.0 Hz, 2H), 4.21 (d, J= 9.0 Hz, 1H), 3.75 (s, 3H), 2.12 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.04-2.02 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester With silver(l) oxide In acetonitrile at 20℃; for 0.0833333h; Stage #2: 4-bromo-2-nitrophenol In acetonitrile at 20℃; for 4h; | 2.22.2 2.22.2. (2S,3R,4S,5S,6S)-2-(4-bromo-2-nitrophenoxy)-6- (methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (2R,3R,4S ,5S ,6S)-2-Bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3 ,4,5-triyl triacetate (5 g) was dissolved in acetonitnle (100 niL). Ag20 (292 g) was added to the solution, and the reaction wasstirred for 5 minutes at room temperature. 4-Bromo-2-nitrophenol (2.74 g) was added, and the reaction mixture was stirred at room temperature for 4 hours. The silver salt residue was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with a gradient of 10-70% ethyl acetate in heptanes, to give the title compound. MS (ESI+) mlz 550.9 (M+NH4). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46.7% | With tetra(n-butyl)ammonium hydrogensulfate; potassium carbonate In dichloromethane; water at 10 - 20℃; for 3h; | 4 4, Synthesis of thymolphtaleine-α-acetyl-D-glucuronic acid methyl ester.It can be expressed by the following reaction formula: preparation steps are: thymolphtaleine (5) (4.3 g, 10 mmol), TBAHS (3.4 g, 10 mmol), acetobromo-α-D-glucuronic acid methyl ester (4) (4.0 g, 10 mmol) dissolved in 30 ml of dichloromethane and cooled to 10 ° C, 30 ml of 1N potassium carbonate aqueous solution was added and then stirred at room temperature for 3 hours, and the mixture was separated and dried over anhydrous sodium sulfate. The organic phase was concentrated to dryness to give thymolphtaleine-α-acetyl-D-glucuronic acid methyl ester (6) (yield: 3.4 g, yield 46.7%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With silver(l) oxide; In acetonitrile; at 20℃; for 16h;Cooling with ice; | To an ice-cold solution of <strong>[400-99-7]2-nitro-4-(trifluoromethyl)phenol</strong> (7.0 mL, 50.36 mmol) in ACN (500 mL) was added silver(I) oxide (37.1 g, 157.4 mmol), followed by the slow addition of a solution of (2R,3R,4S,5S,68)-2-bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (25.0 g, 62.95 mmol) in a minimum amount of ACN. The resulting solution was stirred at room temperature for 16 h and then it was filtered through a pad of diatomaceous earth and washed with EtOAc. The filtrate was concentrated under reduced pressure and the crude residue was purified by column chromatography (30% EtOAc in hexanes) to afford the title compound (25.0 g, 76%) asan off-white solid. |
76% | With silver(l) oxide; In acetonitrile; at 20℃; for 16h;Cooling with ice; | Step 20-1-Preparation of (2S,3S,4S,5R,6S)-2-(Methoxycarbonyl)-6-(2-nitro-4-(trifluoromethyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl Triacetate To an ice-cold solution of <strong>[400-99-7]2-nitro-4-(trifluoromethyl)phenol</strong> (7.0 mL, 50.36 mmol) in ACN (500 mL) was added silver(I) oxide (37.1 g, 157.4 mmol), followed by the slow addition of a solution of (2R,3R,4S,5S,6S)-2-bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (25.0 g, 62.95 mmol) in a minimum amount of ACN. The resulting solution was stirred at room temperature for 16 h and then it was filtered through a pad of diatomaceous earth and washed with EtOAc. The filtrate was concentrated under reduced pressure and the crude residue was purified by column chromatography (30% EtOAc in hexanes) to afford the title compound (25.0 g, 76%) as an off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With silver carbonate; In acetonitrile; at 60℃; | Anomeric bromination of 1 with 33% HBr in acetic acid gave bromide 2 in 70% crystallized yield. Treatment of phenol 3 with bromide 2 in the presence of Ag2CO3in acetonitrile at 60 C. produced compound 4 in 75% yield after reverse phase chromatography. Deprotection of 4 with triethylamine in methanol/water gave clean conversion to glucuronic acid 5 (M15). The reaction was stopped at 90% conversion since the amount of 3 present in the reaction started to increase. The mixture was purified by reverse phase chromatography with 0.1% TFA in the chromatography solvent. The free acid was isolated after lyophilization, however it contained a significant amount of 3. It was discovered that the free acid 5 was unstable in either neutral oracidic conditions. The triethylamine salt of M15 (5) appeared to be stable. Another batch was purified using the same method as before but the TFA was neutralized with triethylamine before lyophilization. The compound was stable to the conditions but contained a large amount of triethylammonium trifluoroacetate. Not all salt was removed. The material was purified by reverse phase chromatography but without TFA in the solvent. After lyophilization the triethylamine salt of M15 (5) was isolated in high purity and 24% overall yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | General procedure: A mixture of alpha4,3-O-isopropylidene pyridoxine, the respective saccharide and molecular sieves (4 A) was stirred under argon atmosphere in dry dichloromethane (5 mL) at rt for 1 h before it was cooled to 0 C. Silver triflate and N-iodosuccinimide (3.0 eq.) were added and the reaction mixture allowed to reach rt overnight. The mixture was diluted with dichloromethane (10 mL) and filtered through a pad of celite. Afterwards, the filtrate was washed with Na2S2O3 (10 % in water, 30 mL) and the aqueous phase was extracted with dichloromethane (3 x 40 mL). The combined organic layers were washed with distilled water (1 x 50 mL), brine (1 x 50 mL) and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product subjected to column chromatography using SiO2 (pentane/ethyl acetate 1/1 to 1/4, gradient elution) followed by C18 (methanol, isocratic) to afford the glycoside, which was used directly in the deprotection reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | Combine acetyl bromide-alpha-D-glucuronic acid methyl ester 5.0 g and<strong>[77-09-8]Phenolphthalein</strong> 4.0 g was added to a round-bottomed flask. After adding 25.0 mL of methanol, 1.46 g of silver oxide was added and reacted at room temperature for 8 h. After the reaction was completed, 2.0 g of NaOH was added while stirring. At room temperature, the reaction was performed for 4 h. After the reaction was completed, 17 mL of 10% was added Hydrochloric acid aqueous solution, adjust the pH to 2-3,After the polar solvent was removed by rotary evaporation, it was purified by a reverse phase column,That is, R1 and R2 are both compounds of the formula II structure of H, that is, <strong>[77-09-8]phenolphthalein</strong> beta-D-glucuronic acid, which is an off-white powder.Yield: 2.18 g; yield: 34%; HPLC content: 99.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | Stage #1: thymolphthalein; 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester With silver(l) oxide In methanol at 20℃; for 8h; Stage #2: With methanol; sodium hydroxide at 20℃; for 4h; | 3-4 Example 3: Add 5.0 g of acetyl bromide-α-D-glucuronate and 4.2 g of thymolphthalein to a round-bottom flask, add 25 mL of methanol and then add 1.46 g of silver oxide, and react at room temperature for 8 h; after the reaction is complete, add while stirring 2.0 g NaOH, react at room temperature for 4 h. After the reaction is completed, add 17 mL of 10% aqueous hydrochloric acid to adjust the pH to 2-3. Rotate to remove the polar solvent and purify by reverse phase column to obtain the product thymolphthalein-β-D-glucose Aldehydic acid, that is, the compound of formula II wherein R1 is a methyl group and R2 is an isopropyl group, is an off-white powder. Yield: 2.3g; yield: 35%; HPLC content: 97%. |
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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.
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