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. : | 1125-88-8 | MDL No. : | MFCD00008491 |
Formula : | C9H12O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HEVMDQBCAHEHDY-UHFFFAOYSA-N |
M.W : | 152.19 | Pubchem ID : | 62375 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.33 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 43.19 |
TPSA : | 18.46 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.12 cm/s |
Log Po/w (iLOGP) : | 2.23 |
Log Po/w (XLOGP3) : | 1.56 |
Log Po/w (WLOGP) : | 1.65 |
Log Po/w (MLOGP) : | 1.93 |
Log Po/w (SILICOS-IT) : | 1.85 |
Consensus Log Po/w : | 1.85 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.97 |
Solubility : | 1.62 mg/ml ; 0.0107 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.56 |
Solubility : | 4.21 mg/ml ; 0.0277 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.68 |
Solubility : | 0.315 mg/ml ; 0.00207 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.25 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H227-H302-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 |
---|---|---|
53.7% | With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 60℃; for 6 h; | Glucose (1.00 g, 5.55 mmol) was added to a N, N-dimethylformamide solution (11.0 mL)It was heated to 60 ° C and dissolved.To this was added benzaldehyde dimethyl acetal (1.24 mL, 8.33 mmol),Paratoluenesulfonic acid monohydrate (10 mg) was added and the mixture was stirred at 60 ° C for 6 hours.The pressure reduction operation was carried out for 10 minutes every hour. After 6 hours, the reaction solution was evaporated under reduced pressure.The obtained residue was subjected to silica gel column chromatography, and as a white crystal from a fraction eluted with methanol / ethyl acetate (1/10)4,6-O-Benzyliden-D-glucopyranose (799.5 mg, 2.98 mmol, yield 53.7percent). As glucose, those of D - (+) - glucose (manufactured by Kanto Kagaku Co., Ltd.) were used. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53.7% | With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 60℃; for 6h; | A suspension of D-glucose (1) (1.00 g, 5.55 mmol) in DMF(11 mL) was heated to 60 C to dissolve the solid. Benzaldehydedimethyl acetal (1.24 mL, 8.33 mmol) and p-toluenesulfonic acidmonohydrate (10 mg) were added. The resulting solution wasstirred at 60 C for 6 h, depressurizing 10 min for each hour in orderto remove MeOH. The mixture was concentrated in vacuo. Theresidue was purified by silica gel column chromatography (MeOH/AcOEt 1:10, v/v) to give glucopyranose 2 (799.5 mg, 2.98 mmol,53.7%) as a white solid.2: [a]20D 12.9 (c 0.20, MeOH); 1H-NMR (400 MHz, CD3OD):d 7.46e7.42 (m, 2H), 7.38e7.35 (m, 3H), 6.31 (d, J 4.1 Hz, 0.5H),5.79 (d, J 7.8 Hz, 0.5H), 5.60 (t, J 9.9 Hz, 0.5H), 5.52 (s, 0.5H), 5.51(s, 0.5H), 5.37 (t, J 9.2 Hz, 0.5H), 5.17e5.10 (m, 1H), 4.39 (dd,J 10.3, 4.6 Hz, 0.5H), 4.32 (dd, J 10.5, 5.0 Hz, 0.5H), 4.08e4.00(m, 0.5H), 3.80e3.63 (m, 2.5H), 2.19 (s, 1.5H), 2.11 (s, 1.5H), 2.08 (s,1.5H), 2.06 (s,1.5H), 2.05 (s,1.5H), 2.04 (s,1.5H); 13C-NMR (100 MHz,CD3OD): d 139.2, 139.1, 129.9, 129.0, 127.5, 103.0, 102.9, 99.0, 94.7,83.1, 82.4, 77.2, 74.7, 74.4, 71.8, 70.3, 69.8, 67.7, 63.5; HRMS (ESI):calcd for C13H16O6Na ([MNa]): 291.0845, found: 291.0842. |
43.3% | With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 60℃; for 5h; | Compound 3 was prepared according to the literature procedure (mp 176-178 C as reported). |
With camphor-10-sulfonic acid; In N,N-dimethyl-formamide; at 20℃; for 25h; | Glucose (90 g) and N, N-dimethylformamide(DMF) (600 ml) were stirred at room temperature,Benzaldehyde dimethyl acetal (90 ml) and camphorsulfonic acid (CSA) (6.18 g) were added in order,And the mixture was stirred at room temperature under reduced pressure for 25 hours.After completion of the reaction, DMF was distilled off under reduced pressure, and triethylamine (4.5 ml) and pyridine (450 ml) were added to and dissolved in the obtained concentrated residue. The solution was cooled to 0 to 5 C.,Acetic anhydride (450 ml) was added, then the temperature was returned to room temperature and stirred for 15 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, toluene was added to the residue, azeotropy was carried out, and pyridine was distilled off. Dichloromethane (600 ml) was added to the obtained concentrated residue and dissolved, and the mixture was washed with saturated aqueous sodium bicarbonate (450 ml) and saturated brine (450 ml), and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the concentrated residue was crystallized from hot methanol to obtain compound (11) (90.75 g, yield 45.9%). |
With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 60℃; for 6h;Inert atmosphere; | To a stirred solution of 44 (15 g, 83.3 mmol) in DMF (150 mL), was added PhCH(OCH3)2 (19 mL, 91.6 mmol, 1.1 eq) p-TSA (0.200 g, 8.33 mmol) and the reaction mixture was stirred at 60 C for 6 h. The mixture was dried under vacuum to obtain compound 45 (10 g, 45%) as a white solid. The combined organic layer was concentrated under reduced pressure crude compound was obtained purified with combi flash eluted with 60% ethyl acetate: Hexane. NMR (400 MHz, CD3OD): d 7.45-7.36 (m, 2H), 7.28-7.21 (m, 3H), 5.46 (s, 0.7H), 5.04 (s, 0.3H), 4.49 (dd, J = 10.8, 4.4 Hz, 0.3H), 4.07 (dd, J = 10.8, 4.4 Hz, 0.7H), 3.90-3.83 (m, 0.7H), 3.77 (t, j = 9.2 Hz, 0.7H), 3.68-3.57 (m, 1.3H), 3.52 (t, j = 9.2 Hz, 0.3H), 3.40-3.30 (m, 2H), 3.17-3.12 (m, 0.3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With camphor-10-sulfonic acid; In dichloromethane; at 20℃; for 19h; | To a stirred solution of triol 1 and benzaldehydedimethyl acetal (5.31 mL, 35.4 mmol) in CH2Cl2 (120 mL) was added CSA (384 mg, 6.10 mmol) at room temperature. After stirring for 19 h at the same temperature, the reaction was quenched with Et3N and the reaction mixture was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel (hexane/AcOEt = 2:1) to give the acetal 3 (5.65 g, 88%) as a colorless oil.1H NMR spectrum of this acetal was identical with that reported.11 1H NMR (300 MHz, CDCl3) "7.54-7.32 (5H, m), 5.54 (1H, s), 4.30 (1H, dd, J = 5.1, 1.2 Hz), 4.03-3.97 (2H, m), 3.68-3.65 (2H, m),2.17 (1H, br s), 2.00-1.76 (1H, m), 1.48-1.45 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With camphor-10-sulfonic acid; In acetonitrile; for 2h;pH 2.0; | To a solution of S11 (1.14 g, 5.09 mmol) and PhCH(OMe)2 (2.30 mL, 15.27 mmol) in CH3CN (35mL), a catalytic amount of camphorsulfonic acid (pH = 2) was added. After 2 h the reaction wasneutralized with TEA and concentrated in vacuo. The crude was purified by flash chromatography(Hexane:AcOEt 1:1) to obtain S12 (1.20 g, 76%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Ethyl 4,6-O-benzylidene-1-thio-β-D-glucopyranose Benzaldehyde dimethyl acetal (14.9 g) and camphorsulfonic acid (1.13 g) were added to a mixture of compound 31 (11 g) in N,N-dimethylformamide (50 mL). The mixture was heated at 60 C. at 189 mbar for 4 hours. The mixture was then cooled to room temperature and triethylamine added to make the mixture basic. The mixture was evaporated under reduced pressure and dissolved in ethyl acetate (200 mL). The mixture was washed with saturated sodium hydrogen carbonate, water and brine, dried (MgSO4) and evaporated under reduced pressure. Crystallisation from ethyl acetate-petrol gave compound 32 (10.5 g). Compound 57; Ethyl 4,6-O-benzylidene-1-thio-β-D-glucopyranoside; Benzaldehyde dimethyl acetal (14.9 g) and camphorsulfonic acid (1.13 g) were added to a mixture of compound 56 (11 g) and dry N,N-dimethylformamide (50 mL). The mixture was heated to 60 C. at 189 mbar for 4 hours. Excess triethylamine was added and the mixture evaporated under reduced pressure. Ethyl acetate was added and the mixture washed with saturated sodium hydrogen carbonate, water and brine, dried (MgSO4) and evaporated under reduced pressure. Crystallisation from ethyl acetate-petrol (2 crops) gave compound 57 (10.5 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 20℃; for 16h; | 3. Synthesis of 1-O-(p-Methoxy phenyl)-4,6-O-benzylidene-beta-D-glucopyranoside; III (RSCL-0370) To Compound II (3.5 g, 12.23 mmol) in anhydrous N,N-dimethylformamide (35 mL) was added dropwise benzaldehyde dimethyl acetal (3.02 mL, 20.17 mmol) followed by addition of p-toluene sulphonic acid (0.2 g). The reaction was stirred at room temperature for 16 h. N,N-Dimethylformamide was removed under high vacuum and the residue was purified using silica gel column (10% methanol/dichloromethane). The organic fractions containing desired product were concentrated and dried under high vacuum (2 mm/Hg) to provide viscous compound III (yield 2.9 g, 85%); Rf 0.45 (15% acetone/dichloromethane); 1H NMR (CDCl3) delta 3.79 (s, 3H), 4.90 (d, 1H, J=7.7 Hz), 5.58 (s, 1H), 6.81 (d, 1H), 6.94 (2d, 1H), 7.36-7.37 (m, 2H), 7.48-7.52 (m, 3H); MS m/z 397 (M+Na)+. Anal. Calculated for C20H22O7: C, 64.16; H, 5.92; O, 29.91. Found: C, 64.08; H, 5.90; O, 30.02 (Slaghek T M, et al. Carbohydr Res. 1994; 255:61-85.) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
STEP 1 : (4aR,6S,7R,8R,8aR)-6-(allyloxy)-2-phenylhexahydropyrano[3,2- d][1,3]dioxine-7,8-diol Into a 3-L 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed (2R,3R,4S,5R,6S)-2-(hydroxymethyl)- 6-(prop-2-en-1 -yloxy)oxane-3,4,5-triol (80 g, 363.27 mmol, 1.00 equiv), CSA (250 mg), (dimethoxymethyl)benzene (82 g, 538.80 mmol, 1.48 equiv), CHCI3 (1.2 L). The resultant suspension was placed in a preheated oil bath (bath temp. 90 C), and the distillate was collected. After approximately 15 ml was collected, the same volume of CHCb was added. This process was repeated. The reaction progress was monitored by TLC. The resulting mixture was washed with 1x500 ml of water and 1x500 ml of saturated aqueous sodium bicarbonate. The resulting mixture was washed with 1x500 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The resulting residue was washed with PE/EA(20: 1) to yield (4aR,6S,7R,8R,8aR)-2-phenyl-6-(prop-2-en-1 -yloxy)-hexahydro-2H-pyrano[3,2- d][1,3]dioxine-7,8-diol as a white solid. 1 H NMR: (300 MHz, CDCI3): delta 7.54- 7.47(m, 2H), 7.41 -7.34(m, 3H), 5.99-5.86(m, 1H), 5.55(s, 1H), 5.34-5.21 (m, 2H), 5.09(s, 1H), 4.29-4.21 (m, 3H), 4.1 1 -4.05(m, 2H), 3.93(s, 2H), 3.74(s, 1H). LC-MS (ES, m/z): 634.2 [2M+NH4] + | ||
With camphorsulfonic acid; In acetonitrile; for 20h; | Small-scale synthesis: To a solution of allyl alpha-D-galactopyranoside (1.0 g, 4.51 mmol) in acetonitrile (25 ml) was added p-methoxybenzaldehyde dimethyl acetal (1.65 g, 9.08 mmol) followed by CSA (105 mg, 0.45 mmol). After 20 h, Et3N (0.1 ml) was added and the solvent was removed under reduced pressure and the residue was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc three times and the combined organic extracts were washed with brine, dried with Na2S04, filtered and concentrated. The residue was purified by flash column chromatography on silica gel (40 g column, EtOAc/heptane: 0>20%>100%, Teledyne ISCO Combiflash) to yield a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53.7% | With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 60℃; for 6h; | Glucose (1.00 g, 5.55 mmol) was added to a N, N-dimethylformamide solution (11.0 mL)It was heated to 60 C and dissolved.To this was added benzaldehyde dimethyl acetal (1.24 mL, 8.33 mmol),Paratoluenesulfonic acid monohydrate (10 mg) was added and the mixture was stirred at 60 C for 6 hours.The pressure reduction operation was carried out for 10 minutes every hour. After 6 hours, the reaction solution was evaporated under reduced pressure.The obtained residue was subjected to silica gel column chromatography, and as a white crystal from a fraction eluted with methanol / ethyl acetate (1/10)4,6-O-Benzyliden-D-glucopyranose (799.5 mg, 2.98 mmol, yield 53.7%). As glucose, those of D - (+) - glucose (manufactured by Kanto Kagaku Co., Ltd.) were used. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | toluene-4-sulfonic acid; In dichloromethane; at 20℃; for 2h; | 100 g (420 mmol) of isopropyl-beta-D-galactopyranoside 49 are suspended in 1 l of methylene chloride and, after adding 100 ml of benzaldehyde dimethyl acetal and 1 g of para-toluenesulfonic acid, stirred at room temperature for 2 hours. After about 2 hours, the reactant has dissolved to give a clear solution. After adding 5 ml of triethylamine, the organic phase is filtered through about 150 ml of silica gel and washed with 500 ml of ethyl acetate. About 700 ml of solvent are removed on a rotary evaporator. The product crystallizes out of this solution within one hour. The product is filtered off with suction and washed with ethyl acetate/n-heptane=1/3. Further concentration of the mother liquor affords a second crystal fraction with somewhat lower purity. 112 g of crystal fraction 1 and 20 g of crystal fraction 2 (total yield 96%) of benzylidene derivative 50 are obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With toluene-4-sulfonic acid; triethylamine; In N,N-dimethyl-formamide; at 20 - 80℃; for 48.0h;Inert atmosphere; | 2-Naphthyl beta-D-glucopyranoside (5) (9.04 g, 29.5 mmol) was dissolved in dry dimethylformamide (50 ml), then benzaldehyde dimethylacetal (8.90 ml, 59 mmol) and pTsOH (0.56 g, 3.0 mmol) were added. The mixture was stirred at 80 oC for 48 h under Ar. After cooling to room temperature, Et3N was added, then the volatiles were removed by vacuum distillation. The residue was dissolved in CHCl3, and the organic solution was washed with saturated NaHCO3 solution. The organic layer was dried, filtered then concentrated in vacuum. The crude product was crystallized from 2-propanol. Yield: 57% (6.65 g); white solid, mp 200-201 oC; [a]22D = -39.2 (c 1, CHCl3); 1H NMR (500 MHz, CDCl3/TMS), d (ppm): 7.80 (dd, J = 11.2, 7.6 Hz, 3H, ArH), 7.58-7.36 (m, 8H, ArH), 7.28 (dd, J = 8.9, 2.6 Hz, 1H, ArH), 5.59 (s, 1H, ArCH); 5.20 (d, J = 7.5, 1H, H-1); 4.43 (dd, J = 10.4, 3.9 Hz, 1H, H-6a), 4.05-3.80 (m, 3H, H-6b, H-4, H-5), 3.94-3.79 (m, 2H, H-4, H-5), 3.74-3.61 (m, 2H, H-2, H-3), 3.01 (s, 1H, OH), 2.94 (s, 1H, OH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With boron trifluoride diethyl etherate; In diethyl ether; at -78 - 20℃; for 4h; | Step A: Boron trifluoride diethyl etherate (12.56 mL, 100 mmol) was added to a -780C solution of N-carbobenzoxy-J/-alanine (4.47 g, 20 mmol) and benzaldehyde dimethyl acetal (2.97 mL, 19.8 mmol) in diethyl ether (100 mL). After stirring at ambient temperature for 4 days, the reaction mixture was recooled to 00C, quenched with saturated aqueous sodium bicarbonate and extracted with diethyl ether. The combined organic extracts were dried (sodium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 5-45% ethyl acetate/hexane afforded benzyl 4-methyl-5-oxo-2-phenyl- 1 ,3-oxazolidine-3-carboxylate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | methanesulfonic acid; In butan-1-ol; at 120℃; for 12h; | 2-(N-ethyl-m-toluidino)-ethanol (108 g, 106 mL, 600 mmol, 2.0 eq), n-butanol (105 mL), benzaldehyde dimethyl acetal (45 mL, 300 mmol, 1 eq), and methane sulfonic acid (3.9 mL, 60 mmol, 0.2 eq) were combined in a 500 mL RBF equipped with magnetic stirring, Dean-Stark apparatus and a reflux condenser. The reaction mixture was a pale-yellow color. The mixture was heated in an oil bath (temperature = 120C) and MeOH was collected in the Dean-Stark trap (11.3 mL). The reaction was complete in less than 12 hours. HPLC analysis gave the following results (12 hours, crude): residual 2-(N-ethyl-m-toluidino)-ethanol (10.4%), product (86%). The reaction was cooled to room temperature and NaOH (1M aq, 60 mL) was added. The mixture was stirred at room temperature for 20 minutes. NH4Cl (sat aq, 20 mL) was added (pH between 6 and 7) and the mixture was diluted with EtOAc (400 mL) and transferred to a separatory funnel. The organics were washed with water (2 x 300 mL) and brine (400 mL), dried (MgSO4), filtered and concentrated to viscous amber oil. The residual BuOH and unreacted starting material was removed by high vacuum distillation (<1 mmHg, 150 C) to afford an amber glass (117.2 g, 87%). The sample was hot transferred to an aluminum foil tray and solidified to a yellow glass. An off-white powder was obtained after crushing and grinding. The product was characterized by 1H and 13C NMR, HPLC, thermal gravometric analysis (TGA), and differential scanning calorimetry (DSC). Sample purity was determined to be about 97% by HPLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium methylate; In N,N-dimethyl-formamide; acetonitrile; at 20℃; under 760.051 Torr; for 16h; | Compound 34: To a solution of 33 in dry co-solvent (DMF and CH3CN) was added benazldehyde dimethylacetal and catalytic amount of sodium methoxide (NaOMe). The reaction was stirred for 16 h at ambient temperature. The solution was neutralized by adding Et3N and concentrated. The mixture was dissolved in ethyl acetate, washed with saturated NaHCO3 solution and brine, dried over MgSO4 and evaporated. The product was recrystallized from a solution of AcOEt-hexanes to give 34 as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In acetonitrile; at 40℃; for 1.5h;Inert atmosphere; | General procedure: To a suspension of the sugar/glycoside (1 mmol) in dry acetonitrile (3 mL) and alpha,alpha-dimethoxytoluene (2 mmol), the organoiridium catalyst (0.03 mmol) was added and the mixture was allowed to stir at 40 C under argon atmosphere till the TLC (n-hexane-EtOAc 2:1) showed complete conversion of the starting material. The work-up and purification of the product were same as Method A. |
77% | With camphor-10-sulfonic acid; In acetonitrile; at 50℃; for 18h; | As can be appreciated from Scheme 7, for synthesis of the trisaccharide hemiacetal form (9), 4-methoxyphenyl beta-D-glucopyranoside (4) (4.0 g, 13.9 mmol) purchased from Tokyo Chemical Industry was dissolved in acetonitrile (70 mL), added with benzaldehyde dimethyl acetal (3.1 mL, 20.9 mmol) and camphorsulfonic acid (323 mg, 1.39 mmol) at room temperature, and agitated at 50 C. for 18 hours. After confirming the completion of the reaction by TLC (chloroform/methanol=10/1, Rf value=0.5), the resultant was neutralized with triethylamine (I mL) (pH 8) and concentrated under a reduced pressure. The resulting residue was crystallized (ethanol) to give Compound 5 (4.0 g, 77%).Compound 5]1H-NMR (CDCl3, 400 MHz) delta 3.58 (m, 1H, H-5), 3.65 (t, 1H, H-4), 3.78 (m, 5H, H-2, H-6, OMe), 3.92 (t, 1H, H-3), 4.38 (dd, 1H, H-6?), 4.92 (d, J=7.6 Hz, 1H, H-1), 5.57 (s, 1H CHPh), 6.84 (dd, 4H, OMePh), 7.49 (m, 5H, Ph); 13C-NMR (CDCl3, 100 MHz) delta 31.1, 55.8, 66.7, 68.8, 73.4, 74.6, 80.5, 102.2, 102.5, 114.8, 118.8, 126.4, 128.5, 129.5, 136.9, 150.9, 155.9 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | General procedure: To an oven-dried round-bottomed flask under N2 atmosphere was added the silyl imidate precursor (1.00 mmol). The flask was charged with CH2Cl2 (5mL) and cooled to 0 C, then amine (1.40 mmol) and TMSOTf (262muL, 322 mg, 1.45 mmol) were added. The mixture was stirred for fifteen minutes at 0C, then acetal (1.4 mmol) was added. The mixture was stirred for 2 h and pyridine (82 mL, 80 mg, 1.0 mmol) was added. The mixture was passed though a plug of silica (1.0 cm x 3.0 cm) with Et2O. The solvent was removed in vacuo, and the residue was purified by column chromatography (10-80% Et2O/hexanes). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With indium(III) triflate; at 20℃; for 0.5h;Neat (no solvent); | General procedure: In(OTf)3 (5.6 mg, 10 mumol, 1 mol %) was added to a mixture of cyclohexanone dimethylacetal (144 mg, 1.00 mmol) and finely ground 2,2-dimethyl-1,3-propanediol (111 mg, 1.10 mmol) and the reaction mixture stirred at room temperature for 30 min. At this time, residual MeOH was removed under reduced pressure and the crude residue passed through a short plug of basic alumina, which was washed with hexane (2×2 mL). The solvent was removed under reduced pressure to give the product, as a colourless oil (170 mg, 92%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Example 1 : Preparation of 2-amino-9-((2-phenyl-l , 3-dioxan-5-yloxy)methyl)-lH-purin- 6(9H)-oneIn a 21t R.B.flask is charged 500ml DMSO and lOOg 2-amino-9-((l,3-dihydroxypropan-2- yloxy)methyl)-lH-purin-6(9H)-one (0.392mol) at temperature of about 25 - 35C, under stirring. The reaction mass is heated at temperature from about 70 to about 80C until all material dissolves. In the above solution is slowly added 129 ml benzaldehyde dimethyl acetal (0.862mol) and 2.6g p-toluenesulfonic acid monohydrate (0.014mol). The reaction mass is stirred at temperature from about 70 to 80 C for about 12-18 hours. Upon completion of the reaction, 20ml triethylamine is charged to the reaction mass and cooled to temperature from about 25 to about 35C. At this temperature 100ml ethyl acetate is added under stirring, and 1500ml D.M. water within 90-150 minutes, keeping the temperature at 25-35C (external cooling is used, if required). The reaction mass is stirred for additional 300-360 minutes. The precipitated solid is filtered off under reduced pressure and sucked dry in the vacuum pump for about 45-60 minutes. The wet cake is transferred into a flask and washed under stirring with 500ml toluene at temperature from about 45 to 55C, for 120-180 minutes. The suspension is cooled to ambient temperature, filtered off under reduced pressure and sucked dry for 30-45 minutes. To the wet cake 100ml ethanol and 500ml D. M. water is added. To the above suspension 120- 160ml aq. sodium hydroxide 20% w/w is slowly added under vigorous stirring, and further stirred for 30-60minutes. To the clear solution is added 100- 150ml hydrochloric acid 3N till adjustment to pH 10-11. The suspension is stirred for additional 60-120minutes at ambient temperature. The precipitated solid is filtered off under reduced pressure and sucked dry in the vacuum pump for 45-60 minutes. The wet solid is washed with 800 ml D.M. water for 60-90 minutes. The solid is filtered again under reduced pressure and sucked dry for 45-60 minutes. The wet cake is unloaded and dried in a vacuum oven at temperature from about 75C to about 85C. Weight of 2-amino-9-((2-phenyl-l,3-dioxan-5-yloxy)methyl)-lH-purin-6(9H)-one is 95-105g (71-78% yield).Analysis of the solid obtained showed:Desired product (benzylidene acetal of Ganciclovir) about 95%Ganciclovir about 0.4%mp: 254.2-254.6C;LC-MS (CI) m/z: 344 (MH+);IR (KBr) cm"1 3455, 3321, 3184, 2858, 2724, 1724, 1690, 1630, 1487, 1389, 1274, 1220, 1182, 1145, 1098, 1028, 755, 698; NMR (300 MHz, DMSO-D6) delta 10.75 (br,lH), 7.92-7.87 (2s, 1H), 7.39-7.31 (m, 5H), 6.58-6.54 (2s,2H), 5.55-5.42 (m, 3H), 4.13-3.48 (m, 5H); 13C NMR (75 MHz, DMSO-D6) delta 156.8-156.7, 153.9-153.8, 151.4-151.2, 138.4-137.6, 137.6-137.4, 128.6-128.4, 127.9-127.8, 126-125.8, 1 16.5-1 16.3, 100.1-99.9, 70.8-69.7, 68.9-68.5, 68.3-66.8. wherein:1H NMR: proton nuclear magnetic resonance spectroscopy13C NMR: carbon nuclear magnetic resonance spectroscopyIR: infrared spectroscopydelta: the chemical shift referenced against tetramethylsilane (TMS)s, d, t and m are referred to singlet, doublet, triplet and multiplet peaks respectively |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33%; 9% | With camphor-10-sulfonic acid; In dichloromethane; at 20℃; for 12h;Reflux; | To a solution of 44 (60 mg, 0.20 mmol) in CH2C12 (2 mL) were added benzaldehyde dimethyl acetal (151 mu, 1.00 mmol) and camphor sulfonic acid (4.7 mg, 0.02 mmol) at rt and the mixture was stirred under reflux condition for 12 h. After addition of sat. aq. NaHC03, the mixture was extracted with AcOEt. The organic layer was washed with brine, dried (Na2S04), and evaporated. The residue was purified by silica gel column chromatography (10-25% AcOEt in hexane) to give 50a (25 mg, 33%, CF3/Ph = anti) as a colorless oil or 50b (7 mg, 9%, CF3/Ph = syn) as a white solid. 50a 1H NMR (500 MHz, CDC13) delta 7.25-7.35 (m, 8H, aromatic), 7.16-7.18 (m, 2H, aromatic), 6.46 (br s, 1H, NH), 5.92 (s, 1H, benzylidene-CH), 4.41 (d, 2H, benzyl-CH2, J= 5.6 Hz), 4.18 (m, 2H, CH2CH20), 2.73 (d, 1Eta, NHC(0)CH2, J= 14.3 Hz), 2.57 (d, 1H, NHC(0)CH2, J= 14.3 Hz), 2.50 (m, 1H, CH2CH20), 1.97 (m, 1H, CH2CH20); 13C NMR (125 MHz, CDC13) delta 167.3, 137.5, 129.4, 128.7, 128.5, 128.0, 127.5, 125.5(q), 98.0, 74.7(q), 63.2, 43.9, 42.8, 25.0; HRMS (pos. ion ESI) m/z calcd for (M+Na)+ C20H20F3NNaO3: 402.1293. Found: 412.1285. 50b 1H NMR (500 MHz, CDC13) delta 7.27-7.38 (m, 8H, aromatic), 7.21-7.23 (m, 2H, aromatic), 6.29 (br s, 1H, NH), 5.78 (s, 1H, benzylidene-CH), 4.49 (dd, 1H, benzyl-CH2, J= 5.9, 14.6 Hz), 4.36 (dd, 1H, benzyl-CH2, J= 5.3, 14.6 Hz), 4.27 (m, 1H, CH2CH20), 4.19 (m, 1Eta, CH2CH20), 3.01 (d, 1Eta, NHC(0)CH2, J= 15.2 Hz), 2.94 (d, 1H, NHC(0)CH2, J= 15.2 Hz), 2.36 (m, 1H, CH2CH20), 2.02 (m, 1H, CH2CH20); 13C NMR (125 MHz, CDC13) delta 167.2, 137.5, 137.0, 129.4, 128.8, 128.4, 127.9, 127.7, 125.9(q), 96.4, 76.0(q), 62.5, 44.0, 36.6, 25.5; HRMS (pos. ion ESI) m/z calcd for (M+Na)+ C20H20F3NNaO3: 402.1293. Found: 412.1283. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.8 g | With toluene-4-sulfonic acid; In toluene; at 80 - 90℃; | 10.3 g of <strong>[13171-64-7]dimethyl D-tartrate</strong> was weighed into a 250 ml three-necked flask, 100 ml of toluene, 17.7 g of benzaldehyde dimethyl acetal, and 600 mg of p-toluenesulfonic acid monohydrate were successively added, the temperature was raised to 80C. to 90C., and the reaction was incubated overnight. Under TLC monitoring, the raw materials were substantially reacted. The reaction solution was quenched with 40 ml of 2 wt % NaHCO3 solution, extracted with MTBE, washed with H2O and saturated brine respectively, dried over anhydrous MgSO4, filtered, concentrated under reduced pressure, and separated by column chromatography to give 4.8 g of white solid (ST0001-001). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In dichloromethane; at 20℃; for 16h; | Butane-1 ,2,4-trioi (1.58 g , 14.9 mrnof) and dimethoxyrnethyi-foenzene (2.64 g,15.9 mmol) in dry DCM (50 ml) were stirred at rt in the presence of CSA (174 mg,0,75 mrnoi) for 16 hours. TEA(144 mg,1.57 mmoi) was then added and the solvents were removed under reduced pressure to yield compound 46.1 (82%) as a colorless oil, which was carried through to the next step without further purification. ' NMR (400 MHz, CDCi3> 6 191 -1.95 ( , 1 H), 2.04-2.14 (m, 1 H), 3.66-3.85 (m, 3 H), 4.1 1 -441 (m, 2 H), 5.45-5.04 (m: 1 H), 7.35-7.40 (m, 3 H), 7.45-7.51 (m, 2 H). US: /z cacd for C.nH,,03 194.1 , found [M+Hf 195,1. {46.2} |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Step 1: 2-((6S,7S,8aS)-6-Ethylsulfanyl-8-hydroxy-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-7-yl)-isoindole-1,3-dione To a solution of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranoside (126 g, 0.26 mol) in anhydrous CH2Cl2 (1100 mL) was added 4A molecular sieves (50 g, ground, activated) and the suspension stirred for 15 minutes at room temperature, EtSH (25.4 mL, 0.34 mol) was charged and the reaction mixture was cooled to 0 C. A solution of BF3·OEt2 (42 mL, 0.34 mol) in anhydrous CH2Cl2 (100 mL) was added dropwise and the mixture allowed to gradually warm up to room temperature over 16 h. The progress of the reaction was monitored by TLC (petrol-acetone 7:3) and required additional amount of EtSH (25.4 mL, 0.34 mol) and BF3·OEt2 (added neat, 42 mL, 0.34 mol), charged at room temperature. The reaction was warmed at 40 C for 3 h, until TLC indicated completion of the reaction. The mixture was filtered and a sat. aq. solution of NaHCO3 followed by solid NaHCO3 were added upon vigorous stirring until evolution of CO2 ceased. The layers were separated and the organic layer was dried (MgSO4), filtered and concentrated in vacuo. The crude mixture was then dissolved in MeOH (700 mL) and NaOMe (25% in MeOH) added to pH 10. The reaction was complete within 2 h as judged by TLC (toluene-acetone 1:1) and was neutralised with Amberlyst15 acidic resin, filtered and concentrated. The resulting white solid was dissolved in 1000 mL of anhydrous CH3CN and PhCH(OMe)2 was added (90 mL, 0.60 mol), followed by p-toluenesulfonic acid (9.9 g, 0.05 mol, pH of the mixture = 3) at room temperature. After 2 h an additional portion of PhCH(OMe)2 (10 mL, 0.07 mol) was added and the reaction was allowed to stir at room temperature for a further 30 minutes, until all the starting material was consumed, as judged by TLC (toluene-acetone 1:1 and 4:1). After neutralisation with Et3N (approx. 10 mL), the solution was concentrated in vacuo. The crude reaction mixture was dissolved in 700 mL of CH2Cl2 and washed with 250 mL of sat. aq. NaHCO3. The layers were separated and the aqueous layer was extracted with CH2Cl2(2 * 100 mL). The combined organic layers were dried (MgSO4) filtered and concentrated in vacuo. The residue was crystallised from AcOEt-Petrol (approximately 2:1 mixture) to give 84.8 g (0.19 mol, 74% over 3 steps) of the benzylidine acetal protected title sugar as a white solid. MS (ESI+) m/z 442 (M+H)+. | |
74% | To a solution of 1, 3, 4, 6-tetra-0-acetyl-2-deoxy-2- phthalimido^-D-glucopyranoside (126 g, 0.26 mol) in anhydrous CH2CI2 (1100 mL) was added 4A molecular sieves (50 g, ground, activated) and the suspension stirred for 15 minutes at room temperature, EtSH (25.4 mL, 0.34 mol) was charged and the reaction mixture was cooled to 0 C . A solution of BF3 -OEt2 (42 mL, 0.34 mol) in anhydrous CH2CI2 (100 mL) was added dropwise and the mixture allowed to gradually warm up to room temperature over 16 h. The progress of the reaction was monitored by TLC (petrol-acetone 7:3) and required additional amount of EtSH (25.4 mL, 0.34 mol) and BF3 -OEt2 (added neat, 42 mL, 0.34 mol), charged at room temperature. The reaction was warmed at 40 C for 3 h, until TLC indicated completion of the reaction. The mixture was filtered and a sat. aq. solution of aHC03 followed by solid aHC03 were added upon vigorous stirring until evolution of CO2 ceased. The layers were separated and the organic layer was dried (MgSC^) , filtered and concentrated in vacuo. The crude mixture was then dissolved in MeOH (700 mL) and NaOMe (25% in MeOH) added to pH 10. The reaction was complete within 2 h as judged by TLC (toluene-acetone 1:1) and was neutralised with Amberlyst15 acidic resin, filtered and concentrated. The resulting white solid was dissolved in 1000 mL of anhydrous CH3CN and PhCH(OMe)2 was added (90 mL, 0.60 mol) , followed by p-toluenesulfonic acid (9.9 g, 0.05 mol, pH of the mixture = 3) at room temperature. After 2 h an additional portion of PhCH(OMe)2 (10 mL, 0.07 mol) was added and the reaction was allowed to stir at room temperature for a further 30 minutes, until all the starting material was consumed, as judged by TLC (toluene-acetone 1:1 and 4:1). After neutralisation with Et3 (approx. 10 mL) , the solution was concentrated in vacuo. The crude reaction mixture was dissolved in 700 mL of CH2CI2 and washed with 250 mL of sat. aq. aHC03. The layers were separated and the aqueous layer was extracted with CH2CI2 (2 x 100 mL) . The combined organic layers were dried (MgSC^) , filtered and concentrated in vacuo. The residue was crystallised from AcOEt-Petrol (approximately 2:1 mixture) to give 84.8 g (0.19 mol, 74% over 3 steps) of the benzylidine acetal protected title sugar as a white solid. MS (ESI+) m/z 442 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With chloro-trimethyl-silane; cobalt(II) chloride; In acetonitrile; at 20℃;Inert atmosphere; | General procedure: To a solution of CoCl2 (0.6 mmol) in anhyd MeCN (4 mL), the selecteddialkyl acetal (1 mmol), TMSCl (1.1 mmol), and butane-1,2,4-triol (3 mmol) were added, with stirring, at r.t. At the end ofthe reaction, the mixture was extracted with EtOAc and the combinedextracts were washed with 5% NaHCO3. The organic layerwas dried (anhyd Na2SO4) and filtered, and the solvent was evaporatedunder vacuum. The oils obtained were purified by flash chromatographyto give the desired compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With camphor-10-sulfonic acid; In dichloromethane; for 12h;Reflux; Inert atmosphere; | To a solution of 29b (60mg, 0.20mmol) in CH2Cl2 (2mL) was added benzaldehyde dimethyl acetal (151muL, 1.00mmol) and camphor sulfonic acid (4.7mg, 0.02mmol) at room temperature, and the mixture was stirred under reflux for 12h. After addition of sat. aq. NaHCO3, the mixture was extracted with AcOEt. The organic layer was washed with brine, dried (Na2SO4), and evaporated. The residue was purified by silica gel column chromatography (10-25% AcOEt in hexane) to give major diastereomer- 32b (25mg, 33%) as a colorless oil or minor diastereomer-32b (7mg, 9%) as a white solid. major-32b: 1H NMR (500MHz, CDCl3) delta 7.25-7.35 (m, 8H, aromatic), 7.16-7.18 (m, 2H, aromatic), 6.46 (br s, 1H, NH), 5.92 (s, 1H, benzylidene-CH), 4.41 (d, 2H, benzyl-CH2, J=5.6Hz), 4.18 (m, 2H, CH2CH2O), 2.73 (d, 1H, NHC(O)CH2, J=14.3 Hz), 2.57 (d, 1H, NHC(O)CH2, J=14.3Hz), 2.50 (m, 1H, CH2CH2O), 1.97 (m, 1H, CH2CH2O); 13C NMR (125MHz, CDCl3) delta 167.3, 137.5, 129.4, 128.7, 128.5, 128.0, 127.5, 125.5(q), 98.0, 74.7(q), 63.2, 43.9, 42.8, 25.0; HRMS (pos. ion ESI) m/z calcd for (M+Na)+ C20H20F3NNaO3: 402.1293. Found: 402.1285. minor-32b: 1H NMR (500MHz, CDCl3) delta 7.27-7.38 (m, 8H, aromatic), 7.21-7.23 (m, 2H, aromatic), 6.29 (br s, 1H, NH), 5.78 (s, 1H, benzylidene-CH), 4.49 (dd, 1H, benzyl-CH2, J=5.9, 14.6Hz), 4.36 (dd, 1H, benzyl-CH2, J=5.3, 14.6Hz), 4.27 (m, 1H, CH2CH2O), 4.19 (m, 1H, CH2CH2O), 3.01 (d, 1H, NHC(O)CH2, J=15.2Hz), 2.94 (d, 1H, NHC(O)CH2, J=15.2Hz), 2.36 (m, 1H, CH2CH2O), 2.02 (m, 1H, CH2CH2O); 13C NMR (125MHz, CDCl3) delta 167.2, 137.5, 137.0, 129.4, 128.8, 128.4, 127.9, 127.7, 125.9(q), 96.4, 76.0(q), 62.5, 44.0, 36.6, 25.5; HRMS (ESI) m/z calcd for [M+Na]+ C20H20F3NNaO3: 402.1287, found: 402.1283. | |
With camphor-10-sulfonic acid; In dichloromethane; for 12h;Inert atmosphere; Reflux; | To a solution of 29b (60mg, 0.20mmol) in CH2Cl2 (2mL) was added benzaldehyde dimethyl acetal (151muL, 1.00mmol) and camphor sulfonic acid (4.7mg, 0.02mmol) at room temperature, and the mixture was stirred under reflux for 12h. After addition of sat. aq. NaHCO3, the mixture was extracted with AcOEt. The organic layer was washed with brine, dried (Na2SO4), and evaporated. The residue was purified by silica gel column chromatography (10-25% AcOEt in hexane) to give major diastereomer- 32b (25mg, 33%) as a colorless oil or minor diastereomer-32b (7mg, 9%) as a white solid. major-32b: 1H NMR (500MHz, CDCl3) delta 7.25-7.35 (m, 8H, aromatic), 7.16-7.18 (m, 2H, aromatic), 6.46 (br s, 1H, NH), 5.92 (s, 1H, benzylidene-CH), 4.41 (d, 2H, benzyl-CH2, J=5.6Hz), 4.18 (m, 2H, CH2CH2O), 2.73 (d, 1H, NHC(O)CH2, J=14.3 Hz), 2.57 (d, 1H, NHC(O)CH2, J=14.3Hz), 2.50 (m, 1H, CH2CH2O), 1.97 (m, 1H, CH2CH2O); 13C NMR (125MHz, CDCl3) delta 167.3, 137.5, 129.4, 128.7, 128.5, 128.0, 127.5, 125.5(q), 98.0, 74.7(q), 63.2, 43.9, 42.8, 25.0; HRMS (pos. ion ESI) m/z calcd for (M+Na)+ C20H20F3NNaO3: 402.1293. Found: 402.1285. minor-32b: 1H NMR (500MHz, CDCl3) delta 7.27-7.38 (m, 8H, aromatic), 7.21-7.23 (m, 2H, aromatic), 6.29 (br s, 1H, NH), 5.78 (s, 1H, benzylidene-CH), 4.49 (dd, 1H, benzyl-CH2, J=5.9, 14.6Hz), 4.36 (dd, 1H, benzyl-CH2, J=5.3, 14.6Hz), 4.27 (m, 1H, CH2CH2O), 4.19 (m, 1H, CH2CH2O), 3.01 (d, 1H, NHC(O)CH2, J=15.2Hz), 2.94 (d, 1H, NHC(O)CH2, J=15.2Hz), 2.36 (m, 1H, CH2CH2O), 2.02 (m, 1H, CH2CH2O); 13C NMR (125MHz, CDCl3) delta 167.2, 137.5, 137.0, 129.4, 128.8, 128.4, 127.9, 127.7, 125.9(q), 96.4, 76.0(q), 62.5, 44.0, 36.6, 25.5; HRMS (ESI) m/z calcd for [M+Na]+ C20H20F3NNaO3: 402.1287, found: 402.1283. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With camphor-10-sulfonic acid; In N,N-dimethyl-formamide; at 60℃; | A 250 ml round bottom flask is added 20.44g (50mmol) compound II - 1, 22.83g (150mmol) benzene formaldehyde dimethyl acetal, 3g camphor sulfonic acid (CSA) and 120 ml dry DMF, then heating at 60 C under stirring overnight, TLC shows the reaction is complete.The reaction mixture is cooled to room temperature to be dumped after to the 400 ml ice water, stirring, for 200 ml × 3 methylene chloride extraction. The combined organic phase, are saturated NaHCO3Solution and salt water washing, drying with anhydrous sodium sulfate, the solvent on the rotary evaporator, the residue obtained after column chromatography purification, to obtain the product III - 1. |
With camphor-10-sulfonic acid; In N,N-dimethyl-formamide; at 110℃; for 3h;Inert atmosphere; | 4.09 g (10 mmol) of compound 1, 1.83 g (12 mmol) of benzaldehyde dimethyl acetal and 0.1 gram of CAS (camphorsulfonic acid) is dissolved in 30 mL of dry DMF, heated and stirred for 3 hours at 110C under nitrogen atmosphere. After cooling the reaction mixture is diluted with 150 mL of dichloromethane, washed successively with 20 mL of 5% sodium carbonate solution and saturated salt water, and dried with anhydrous sodium sulfate. The drying agent is removed by filtration, the solvent in the filtrate is removed on the rotary evaporator, and the resulting residue is purified by silica gel column chromatography to obtain the pure product 7, a white solid. Melting point 176-178C. 1H NMR (DMSO-d6, 400 MHz), delta 7.45-7.47 (m, 2H), 7.36-7.40 (m, 4H), 7.28 (d, 1H, J = 1.6 Hz), 7.21 (dd, 1H, J = 2.0 Hz and 8.4 Hz), 7.08 (d, 2H, J = 8.8 Hz), 6.83 (d, 2H, J = 8.4 Hz), 5.60 (s, 1H), 5.31 (d, 1H, J = 3.6 Hz), 5.13 (d, 1H, J = 5.6 Hz), 4.16-4.22 (m, 2H), 3.94-3.99 (m, 4H), 3.65-3.70 (m, 1H), 3.50-3.51 (m, 3H), 3.24-3.28 (m, 1H), 1.29 (t, 3H, J = 6.8 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; | The compound 2?-C-methyluridine is treated with an acetal such as benzaldehyde dimethyl acetal, and an acid catalyst such as p-toluenesulfonic acid to generate acetal 3. Compound 3 is oxidized with an oxidizing agent such as pyridinium dichromate in the presence of an alcohol such as tert-butanol, an anhydride such as acetic anhydride and an organic solvent such as dichloromethane. The ester is reduced with a reducing agent such as sodium borodeuteride in a combination of protic solvents such as EtOD and D2O optionally at an elevated temperature. Compound 5 is treated with the phosphoramidate from Example 20, a Grignard reagent such as tert-butylmagnesium bromide in an organic solvent such as tetrahydrofuran optionally at a reduced temperature. The acetal is treated with an acid such as trifluoroacetic acid in an organic solvent such as dichloromethane to afford the product. The acetal can also be treated with a catalyst such as Pd(OH)2 in an organic solvent such as cyclohexene to afford the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With toluene-4-sulfonic acid; In acetonitrile; at 20℃; for 0.333333h; | <strong>[461432-26-8](2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol</strong>(type IV compounds of structure shown in the) (5.02g, 12 . 2mmol, tianjin pharmaceutical research Institute), P-toluenesulfonic acid monohydrate (0.91g, 5 . 02mmol, Guangzhou launching chemical reagent Company limited) is dissolved in acetonitrile (50 ml) in, adding benzaldehyde dimethyl acetal (5.60g, 12 . 7mmol, aladin) acetonitrile solution (40 ml), the reaction stirred at room temperature 20 minutes, then add 20 ml saturated sodium bicarbonate solution quenching the reaction, by adding dichloromethane (50mLx2) extraction, the organic layer is dried with anhydrous sodium sulfate, filtered and concentrated. The obtained residue with petroleum ether (20 ml) of recrystallization, to obtain white solid shows structure of the compounds of formula V (6.02g, 99.0%). |
98.7% | With toluene-4-sulfonic acid; In acetonitrile; at 20℃; for 0.333333h; | The (2S, 3R, 4R, 5S, 6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]benzyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol 1a (5.00g, 12.22mmol, Using J.Med. Chem.2008; 51 (5); the method described prepared 1145-1149), p-toluenesulfonic acid hydrate (0.90 g, 4.73mmol, Guangzhou large chemical reagentsCo., Ltd.) was dissolved in acetonitrile (50mL) was added benzaldehyde dimethyl acetal (5.60g, 36.80 mmol,Aladdin) in acetonitrile (40 mL), the reaction was stirred at room temperature for 20 minutes, followed by theaddition of saturated sodium bicarbonate solution (20 mL of) the reaction was quenched by adding dichloromethane (50mL x2) and the combined organic layers were combined dried over anhydrous sodium sulfate, filtered, and concentrated The residue was treated with petroleum ether (20 mL) and recrystallized to give the title compound 1b (6.02g, white solid), yield: 98.7%. |
95% | With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 100℃;Inert atmosphere; | Step 1: (4aR, 6S, 7R, 8R, 8aS) -6- (4-chloro-3- (4-ethoxybenzyl) phenyl) -2-phenylhexahydropyrano [3, 2-d] [1, 3] dioxine-7, 8-diol (4a) To a mixture of <strong>[461432-26-8]dapagliflozin</strong>, 24 (1.05 g, 2.57 mmol) , benzaldehyde dimethyl acetal (0.58 mL, 3.86 mmol) , and catalytic p-toluenesulfonic acid (49 mg, 0.26 mmol) was added anhydrous DMF (15 mL) , which was stirred at 100under N2overnight. Concentrated the solvent and purified by flash column chromatography (silica gel, EtOAc:PE 1:51:1) , 1.21 g of 4a was obtained as a white solid, yield: 95.1H NMR (400 MHz, CDCl3) delta 7.52-7.51 (m, 2H) , 7.37-7.35 (m, 4H) , 7.21-7.17 (m, 2H) , 7.12 (d, J 8.4 Hz, 2H) , 6.83 (d, J 8.4 Hz, 2H) , 5.51 (s, 1H) , 4.32-4.29 (m, 1H) , 4.13-3.96 (m, 5H) , 3.76-3.68 (m, 2H) , 3.55-3.43 (m, 3H) , 1.40 (t, J 6.8 Hz, 3H) 13C NMR (100 MHz, CDCl3) delta 162.88, 157.40, 139.00, 137.17, 137.13, 134.11, 131.14, 130.40, 129.85, 129.56, 129.23, 128.33, 126.49, 126.39, 114.48, 101.76, 81.77, 80.92, 75.46, 74.77, 70.69, 68.77, 63.37, 38.42, 14.89 LC-MS (ESI) m/z: calcd for [C28H29ClO6H+] , 497.17, found 497.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium methylate; In N,N-dimethyl-formamide; acetonitrile; at 20℃; for 16h; | To a solution of 33 in dry co-solvent (DMF and CH3CN) was added benazldehyde dimethylacetal and catalytic amount of sodium methoxide (NaOMe). The reaction was stirred for 16 h at ambient temperature. The solution was neutralized by adding Et3N and concentrated. The mixture was dissolved in ethyl acetate, washed with saturated NaHCO3 solution and brine, dried over MgSO4 and evaporated. The product was recrystallized from a solution of AcOEt-hexanes to give 34 as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Ca. 97% | With graphene; In neat (no solvent); at 100℃; for 10h;Sealed tube; | General procedure: A mixture of diol 1 (1mmol), benzaldehyde dimethyl acetal (1.25mol) and graphene (6mg) were stirred for 10h at 100C. The resulting mixture was filtered on a nylon membrane, washed with a minimum amount of acetone and the crude was carefully concentrated under vacuum giving the corresponding cyclic acetal in excellent purity (>90%) without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With trimethylsilyl trifluoromethanesulfonate; In acetonitrile; at 20℃; for 16h;Inert atmosphere; | To an oven-dried round-bottomed flask under N2 atmosphere was added MeCN (5 mL), acetal (1.0 mmol), and <strong>[18293-53-3](trimethylsilyl)acetonitrile</strong> (192 mL, 159 mg, 1.40 mmol). To the stirring solution was added dropwise trimethylsilyl trifluoromethanesulfonate (217 mL, 266 mg, 1.20 mmol) and the reaction was stirred overnight. The reaction mixture was diluted with Et2O (30 mL) and saturated NaHCO3 (30 mL). The layers were separated and the aqueous layer was back extracted with Et2O (30 mL). The combined organic layers were dried over MgSO4, then filtered through a cotton plug. The solvent was removed in vacuo and the residue was purified by column chromatography (2-5% EtOAc/hexanes). 3-Methoxy-3-phenylpropanenitrile (1a) was prepared according to the General Procedure, using benzaldehyde dimethyl acetal (150 muL, 152 mg, 1.00 mmol) as the electrophile. The product was isolated as a yellow oil (138 mg, 85%): IR (film) 3038, 2942, 2831, 2256, 1498, 1458, 1186, 1100, 1011, 855, 758, 700 cm-1; 1H NMR (500 MHz, CDCl3) delta 7.46 - 7.40 (m, 2H), 7.40 - 7.34 (m, 3H), 4.47 (dd, J = 7.2, 5.5 Hz, 1H), 3.32 (s, 3H), 2.78 (dd, J = 16.7, 7.2 Hz, 1H), 2.71 (dd, J = 16.6, 5.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) delta 138.6, 128.91, 128.87, 126.3, 117.1, 78.9, 57.1, 26.9; HRMS (EI, TOF) exact mass calcd for C10H11NONa [M+Na]+, 184.0733. Found: 184.0733. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 70℃; for 14h; | To a stirred solution of <strong>[497-76-7]arbutin</strong> (10 mmol, 2.7 g) in DMF (10 mL) was added benzaldehyde dimethyl acetal (12 mmol, 1.8 mL) and a catalytic amount of p-TsOH at room temperature. The reaction is heated up to 70 C and stirred for 14 h. H2O (30 mL) was then added, the white precipitate was filtrated and dried under vacuum to afford the title product as a white solid (3.0, 84 % yield). MP: 247-248 C Rf: 0.6 (50% Acetone/hexane), [alpha]21D -40.3 (c 0.60, acetone); MP: 247.1-248.5 C; IR (ATR) 3336, 1509, 1376, 1215, 1081, 1016, 748, 695 cm-1; 1H NMR (500 MHz, (CD3)2CO) delta 8.15 (s, 1H), 7.64-7.46 (m, 2H), 7.47-7.33 (m, 3H), 7.09-6.90 (m, 2H), 6.92-6.68 (m, 2H), 5.67 (s, 1H), 5.00 (d, J = 7.7 Hz, 1H), 4.80 (d, J = 4.3 Hz, 1H), 4.70 (d, J = 3.9 Hz, 1H), 4.32 (dd, J = 10.3, 4.7 Hz, 1H), 3.99-3.71 (m, 2H), 3.71-3.54 (m, 3H).13C NMR (125 MHz, (CD3)2CO) delta 153.3, 151.4, 138.7, 129.1, 128.4, 126.9, 118.7, 116.0, 103.2, 101.8, 81.4, 75.3, 74.0, 68.8, 66.8. HRMS (ESI) m/z:[M+Na]+ cacld for C19H20O7383.1101; Found 383.1191. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In ethanol; water;Reflux; | General procedure: One equiv. of protected hydrazine was dissolved/suspended in EtOH containing 10percent water (approx. 5 ml per 1 mmol of protected hydrazine), 1.05 eq of benzaldehyde acetal was added, followed by the addition of 0.05 equiv. of TsOH in an ethanolic solution (10 mg of TsOH per 0.5 ml of EtOH). The obtained reaction mixture was refluxed and monitored by TLC (silica gel) until full conversion of the starting material was observed. Ethyl acetate/light petroleum mixtures or pure ethyl acetate were used as TLC eluents. After completion of the reaction the solvent was removed under reduced pressure, approx. 15 ml of toluene was added to the residue and the solvent was again removed under reduced pressure. The obtained crude hydrazone was dissolved in commercial stabilized THF (approx. 4 ml per 1mmol of hydrazone), the flask was flushed with argon and 3 equiv. of 1M BH3-THF complex was added at room temperature, followed by 3 hours of stirring. The progress of the reaction was checked by TLC and if some unreacted hydrazone was left, stirring was continued for an additional 45 min. After thefull conversion of hydrazone EtOH (10 ml) was added to the reaction mixture (Caution: Liberation of hydrogen) and the obtained mixture was refluxed for 1 hour. After cooling to room temperature the solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate, washed with saturated NaHCO3 solution, water and saturated NaCl solution. The aqueous phase was extracted twice with ethyl acetate, the extracts were washed with saturated NaCl solution, combined with the organic phase, dried over anhydrous Na2SO4 and evaporated to dryness. The residue was purified by column chromatography on silica gel by using ethyl acetate/light petroleum 1:1 or 1:2 mixtures or pure ethyl acetate as eluent. For the exact information about the eluent used for monitoring reaction progress and chromatographic purifications, see the Rf value for each compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With lipase from Candida cylindracea; In toluene; at 50℃; for 96h;Enzymatic reaction;Catalytic behavior; | General procedure: An acetal 1a-u (1.5 mmol) was added to the suspension of enzyme(30 mg) in toluene (1 mL), followed by addition of cyanoacetic acid(0.5 mM). The reaction mixture was incubated at 150 rpm at 50 for 4 days. Then the enzyme was filtered off and toluene was evaporated invacuo. The resulting residue was purified by column chromatography(silica gel, eluent ethyl acetate/hexanes) to obtain desired product 5a-u |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Compound 7 (0.332 g, 0.908 mmol) was dissolved in DMF (10 mL) under nitrogen, followed byadding benzaldehyde dimethyl acetal (204 L, 1.36 mmol) and a catalytic amount of p-toluene sulfonicacid. The reaction mixture was stirred for 2.5 h at room temperature and reaction completion wasconrmed by TLC. Then the solution was diluted with ethyl acetate (20 mL) and washed successivelywith H2O (2 10 mL) and brine (20 mL). The organic layer was separated, dried (Na2SO4) andevaporated as pale yellow syrup, which was pure enough to proceed to the next step. The compound(260 mg, 0.57 mmol) was dissolved in THF (30 mL) to which Bu2SnCl2 (17 mg, 0.057 mmol) was addedunder nitrogen atmosphere and the mixture was stirred at room temperature for 15 min. A mixtureof 1,1,2,2,6-pentamethylpiperidine (260 L, 1.14 mmol) and 3,5-bis-(trifluoromethyl)benzenesulfonylchloride (197 mg, 0.63 mmol) in THF, was added to it. The mixture was stirred overnight at roomtemperature until the starting material was completely consumed (TLC). The solution was quenchedby NH4Cl solution and the solvents were evaporated to give the crude product. The solution was thendiluted with ethyl acetate (20 mL) and washed successively with H2O (2 10 mL) and brine (10 mL).The organic layer was separated, dried (Na2SO4) and evaporated in vacuo. The crude product waspurified by flash chromatography (SiO2, heptane:EtOAc 1:1) to aord pure 15 (216 mg, 52%) as whitefoam. []D25 + 6.2 (c 0.56 in CHCl3), 1H NMR (400 MHz, CDCl3) : 8.45 (s, 2H, ArH), 8.24 (d, 1H, J 8.0Hz, ArH), 8.10-8.07 (m, 2H, ArH), 7.54 (t, 1H, J 7.2 Hz, ArH), 7.45-7.33 (m, 5H, ArH), 7.24 (dd, 2H, J8.0, 7.2 Hz, ArH), 6.67-6.61 (m, 2H, ArH), 5.58 (s, 1H, CHPh), 4.78 (dd, 1H, J 3.2 Hz, H-3), 4.56 (d, 1H, J3.2 Hz, H-4), 4.36-4.25 (m, 3H, CH2NH, H-2, H-6a), 4.08-4.02 (m, 2H, H-5, H-6b), 3.58 (s, 2H, OH),3.46 (d, 1H, J 9.6 Hz, H-1), 3.33-3.27 (m, 1H, CH2NH). 13C NMR (100 MHz, CDCl3) : 171.4, 161.6,159.1, 139.6, 137.4, 132.9, 132.6, 131.82, 131.8, 129.2, 128.7, 128.4, 127.1, 126.4, 126.3, 126.0, 125.1, 124.1,123.88, 123.85, 121.1, 121.0, 120.9, 108.6, 108.4, 100.5, 83.0, 79.5, 75.3, 69.6, 69.2, 64.5, 40.2. HRMS calcdfor C33H26F7NO8SNa (M + Na)+: 752.1165, found: 752.1170. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With chloro-trimethyl-silane; NiCl2 * 4 pyridine; zinc; [C(CH3)=N-(2-(t-Bu)C6H4)]2; In N,N-dimethyl acetamide; at 30℃; for 24h;Inert atmosphere; Sealed tube; Glovebox; | General procedure: An oven-dried 10 mL reaction tube equipped with a magneticstir bar was introduced to an argon-filled glove box. NiCl2·Py4 (11.3 mg, 0.025 mmol, 5 mol%), L1 (8.8 mg,0.025 mmol, 5 mol%), zinc (97.5 mg, 1.5 mmol, 3.0 equiv.)and anhydrous N,N-dimethylaniline (DMA) (2 mL) wereadded in this order. Then acrylate (0.5 mmol, 1.0 equiv.), aryliodide (0.75 mmol, 1.5 equiv.), acetal (0.5 mmol, 1.0 equiv.)and chlorotrimethylsilane (TMSCl) (190 μL, 1.5 mmol, 3.0equiv.) were added to the resulting mixture. The tube wassealed with a rubber stopper, and stirred at 30 C for 24 h.After the reaction was complete, water (10 mL) was added,and then extracted with ethyl acetate (10 mL×3). The combinedorganic layers were dried over Na2SO4 and concentratedunder reduced pressure. The residue was purifiedby column chromatography using petroleum ether and ethylacetate as eluent, to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With chloro-trimethyl-silane; [dMeObpy]NiCl2; zinc; In 1-methyl-pyrrolidin-2-one; at 30℃; for 24h;Inert atmosphere; Sealed tube; | General procedure: Under argon atmosphere, into an oven-dried 10 mL reactiontube equipped with a magnetic stir bar and sealed with arubber stopper sequentially added [Ni]-1 (12.9 mg,0.0375 mmol, 7.5 mol%) and anhydrous N-methyl-2-pyrrolidinone(NMP) (2 mL). The mixture was stirred at 30 C for30 min, and then acylate (1.0 mmol, 2.0 equiv.), acetal(1.0 mmol, 2.0 equiv.), aryl iodide (0.5 mmol, 1.0 equiv.),zinc (97.5 mg, 1.5 mmol, 3.0 equiv.) and chlorotrimethylsilane(TMSCl) (158 μL, 1.25 mmol, 2.5 equiv.) were addedin this order. The resulting mixture was stirred at 30 C for24 h. After the reaction was complete, water (10 mL) wasadded, and then extracted with ethyl aceate (10 mL×3). Thecombined organic layers were dried over Na2SO4 and concentratedunder reduced pressure. The residue was purifiedby column chromatography using petroleum ether and ethylacetate as eluent, to afford the desired product. |
Tags: 1125-88-8 synthesis path| 1125-88-8 SDS| 1125-88-8 COA| 1125-88-8 purity| 1125-88-8 application| 1125-88-8 NMR| 1125-88-8 COA| 1125-88-8 structure
[ 127657-97-0 ]
Benzyloxyacetaldehyde dimethyl acetal
Similarity: 0.86
[ 2425-41-4 ]
(2-Phenyl-1,3-dioxane-5,5-diyl)dimethanol
Similarity: 0.84
[ 2568-25-4 ]
Benzaldehyde Propylene Glycol Acetal
Similarity: 0.82
[ 127657-97-0 ]
Benzyloxyacetaldehyde dimethyl acetal
Similarity: 0.86
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 :