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CAS No. : | 838-85-7 | MDL No. : | MFCD00003033 |
Formula : | C12H11O4P | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ASMQGLCHMVWBQR-UHFFFAOYSA-N |
M.W : | 250.18 | Pubchem ID : | 13282 |
Synonyms : |
DPhP
|
Num. heavy atoms : | 17 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 4 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 63.97 |
TPSA : | 65.57 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.85 cm/s |
Log Po/w (iLOGP) : | 1.87 |
Log Po/w (XLOGP3) : | 1.38 |
Log Po/w (WLOGP) : | 3.24 |
Log Po/w (MLOGP) : | 2.23 |
Log Po/w (SILICOS-IT) : | 1.76 |
Consensus Log Po/w : | 2.1 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -2.52 |
Solubility : | 0.757 mg/ml ; 0.00303 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.36 |
Solubility : | 1.09 mg/ml ; 0.00436 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.84 |
Solubility : | 0.0359 mg/ml ; 0.000144 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 0.0 |
Synthetic accessibility : | 3.4 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | 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 |
---|---|---|
83% | With water In tetrahydrofuran at 65℃; for 2h; | |
With 1H-imidazole; water In acetonitrile at 25℃; var. imidazoles and pyridines, and solvents; | ||
With water |
With potassium carbonate | ||
With water | ||
With water In acetonitrile at 25℃; | ||
With water; formamide In acetonitrile at 25℃; | ||
With water for 24h; | ||
Multi-step reaction with 2 steps 2: tetraethylammonium hydroxide / acetonitrile; H2O / 20 °C / Variation of the velocity constant with various concentration of water. | ||
Multi-step reaction with 2 steps 1: pyridine; benzene 2: lithium chloride; 2-ethoxy-ethanol | ||
6.5 g | With water In acetone for 1h; Reflux; | a 2.1. General procedures for the synthesis of diaryl hydrogenphosphates 2-15 General procedure: Method B differs from method A by product purification byextraction without recrystallisation (hydrolysis in pyridine or ace-tone). After hydrolysis, the ester was dissolved in a solution ofpotassium carbonate (6.9 g) in water (50 mL). The resulting solu-tion was washed with chloroform to remove impurities, thenorthophosphoric acid (5.0 mL) was added, and the product wasextracted with dichloromethane (2 × 20 mL). The extract was driedwith anhydrous sodium sulphate and concentrated. |
Multi-step reaction with 2 steps 1.1: trimethylamine / tetrahydrofuran / 0 - 20 °C 2.1: o-phthalic dicarboxaldehyde; monoammonium para-toluenesulfonate; water / acetonitrile / 24 h / 90 °C / Sealed tube 2.2: pH 1 - 2 | ||
Multi-step reaction with 2 steps 1.1: trimethylamine / tetrahydrofuran / 0 - 20 °C 2.1: o-phthalic dicarboxaldehyde; monoammonium para-toluenesulfonate; water / acetonitrile / 24 h / 90 °C / Sealed tube 2.2: pH 1 - 2 | ||
Multi-step reaction with 2 steps 1.1: trimethylamine / tetrahydrofuran / 0 - 20 °C 2.1: o-phthalic dicarboxaldehyde; monoammonium para-toluenesulfonate; water / acetonitrile / 24 h / 90 °C / Sealed tube 2.2: pH 1 - 2 | ||
Multi-step reaction with 2 steps 1.1: trimethylamine / tetrahydrofuran / 0 - 20 °C 2.1: o-phthalic dicarboxaldehyde; monoammonium para-toluenesulfonate; water / acetonitrile / 24 h / 90 °C / Sealed tube 2.2: pH 1 - 2 | ||
Multi-step reaction with 2 steps 1.1: trimethylamine / tetrahydrofuran / 0 - 20 °C 2.1: o-phthalic dicarboxaldehyde; monoammonium para-toluenesulfonate; water / acetonitrile / 24 h / 90 °C / Sealed tube 2.2: pH 1 - 2 | ||
Multi-step reaction with 2 steps 1.1: trimethylamine / tetrahydrofuran / 0 - 20 °C 2.1: o-phthalic dicarboxaldehyde; monoammonium para-toluenesulfonate; water / acetonitrile / 24 h / 90 °C / Sealed tube 2.2: pH 1 - 2 | ||
Multi-step reaction with 2 steps 1.1: trimethylamine / tetrahydrofuran / 0 - 20 °C 2.1: o-phthalic dicarboxaldehyde; monoammonium para-toluenesulfonate; water / acetonitrile / 24 h / 90 °C / Sealed tube 2.2: pH 1 - 2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | for 0.00555556h; Microwave irradiation; neat (no solvent); | |
90% | With water In acetonitrile for 4h; Ambient temperature; | |
87% | for 0.0833333h; ground in mortar; Neat (no solvent); |
In water; acetonitrile at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | In dichloromethane for 6.5h; Ambient temperature; | |
63% | In dichloromethane; phosphoric acid dibenzyl ester | 6 EXAMPLE 6 EXAMPLE 6 A solution of O-(2,3,4-tri-O-acetyl-α-L-fucopyranosyl) trichloroacetimidate (0.50 g, 1.15 mmol) in dry dichloromethane (25 ml) and commercially available diphenyl phosphate which is not purified further (0.29 g, 1.16 mmol) is stirred under nitrogen at room temperature for about 6.5 h. In the case of very pure dibenzyl phosphate, a catalytic amount of boron trifluoride is added to the mixture. The solution is then concentrated and purified by chromatography (petroleum ether/diethyl ether 1:5). Diphenyl 2,3,4-tri-O-acetyl-α-L-fucopyranosyl phosphate (4) is obtained in a yield of 63% as a colorless oil (0.38 g). TLC (petroleum ether/diethyl ether 1:5) gives an Rf of 0.41. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With N,N,N',N'-tetramethylchlorformamidinium chloride; triethylamine In dichloromethane at 0 - 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium fluoride; trifluoroacetic anhydride In dimethyl sulfoxide; acetonitrile at 60℃; for 11h; Inert atmosphere; | 18 Using diphenyl phosphate and sodium fluoride as raw materials, the reaction formula and experimental steps are as follows:Take diphenyl phosphate (75mg, 0.3mmol) and sodium fluoride (15.1mg, 0.36mmol) into a 10mL reaction tube, use a double-row tube to replace the air in the reaction tube with nitrogen, replace it three times, and then add to it in sequence 2mL acetonitrile, trifluoroacetic anhydride (189mg, 0.9mmol), DMSO (24mg, 0.3mmol), the reaction was placed in an oil bath at 60°C for 11 hours. After the reaction, the reaction solution was concentrated, and the mixture of petroleum ether and ethyl acetate with a volume ratio of 3:1 was used as the eluent, and the product diphenoxyphosphoryl fluoride was separated by column chromatography, and the yield was 82%. |
77% | With sodium fluoride; dimethyl sulfoxide; trifluoroacetic anhydride In acetonitrile at 60℃; for 11h; Inert atmosphere; | |
52 % Spectr. | With N,N-dimethyl-1-fluoro-2-methylpropenamine In 1,1,2,2-tetrachloroethane at 120℃; for 0.0833333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.3% | With bis(trichloromethyl) carbonate In dichloromethane; N,N-dimethyl-formamide at 10℃; for 3h; | 1;2 Example 1 With a thermometer,Reflux condenser and mechanical agitation120 g of dichloromethane was placed in a 500 ml four-neck reaction flask.7.3 g of N,N-dimethylformamide,Stirring temperature control below 10 °C,Put 28g of bis(trichloromethyl) carbonate,A solution of 50 g of diphenyl phosphate and 120 g of dichloromethane was added.After the addition, the reaction was carried out for 3 hours. After the end of the reaction, the temperature was controlled below 10 ° C, 20 g of water was slowly added, and the mixture was stirred and the organic phase was dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and the filtrate was evaporated under normal pressure. The temperature was lowered to 0 ° C, and the insoluble matter was removed by filtration to obtain 48.9 g of diphenyl chlorophosphate. The purity of GC was 99.2%, and the yield was 90.3%. |
57 % Spectr. | With 1-chloro-1-(dimethylamino)-2-methyl-1-propene In 1,1,2,2-tetrachloroethane at 120℃; for 0.0833333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With copper(l) iodide; sodium carbonate; triethylamine In tetrachloromethane at 80℃; for 12h; | |
89% | With tetrachlorosilane at 0℃; | |
42% | With dicyclohexyl-carbodiimide In 1,4-dioxane at 20℃; for 6h; Inert atmosphere; | General procedure General procedure: A mixture of P(O)OH compounds (0.5 mmol), alcohol (0.5 mmol), and DCC (0.55 mmol) was dissolved in dioxane under N2 atmosphere, stirred at room temperature for 6h. Removal of the solvent under a reduced pressure gave the crude product; pure product was obtained by passing the crude product through a short silica gel column using Hexane/EtOAc (1:1-5:1) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With pyridine; trichloroacetonitrile; triphenylphosphine In dichloromethane at 20℃; for 5.5h; | |
90% | With tetrachlorosilane at 0℃; | |
89% | With p-TsOH-Celite at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With pyridine; trichloroacetonitrile; triphenylphosphine In dichloromethane at 20℃; for 5.5h; | |
88% | With tetrachlorosilane at 0℃; | |
87% | With p-TsOH-Celite at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With tetrachlorosilane at 0℃; | |
91% | With copper(l) iodide; sodium carbonate; triethylamine In tetrachloromethane at 80℃; for 12h; | |
90% | With p-TsOH-Celite at 20℃; |
88% | With pyridine; trichloroacetonitrile; triphenylphosphine In dichloromethane at 20℃; for 5.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With p-TsOH-Celite at 20℃; | |
92% | With pyridine; trichloroacetonitrile; triphenylphosphine In dichloromethane at 20℃; for 5.5h; | |
90% | With tetrachlorosilane at 0℃; |
89% | With copper(l) iodide; sodium carbonate; triethylamine In tetrachloromethane at 80℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With dmap; toluene In dichloromethane at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium fluoride In Isopropyl acetate at 60℃; for 1.25h; | 78.1 Example 78-1; Diphenyl anilino(4-cyanophenyl)methylphosphonate To a solution of 4-formylbenzonitrile (175g) in isopropyl acetate (2. 1L) was added potassium fluoride (77. 5mg) followed by addition of aniline (124G), and the mixture was heated TO 60C with stirring. To the mixture WAS ADDED DROPWISE DIPHENYLPHOSPHONATE (469g) OVER45MIN, and the mixture was heated at 60C for additional 30min. To the mixture was added dropwise n-heptane (2.8L) over 2hrs, and the mixture was cooled to 15C. The resulting precipitate was collected by filtration, washed successively with water, 50% isopropyl acetate in n-heptane, and dried to give the title compound as crystals (494g, 84%). H-NMR (300MHZ, DMSO-D6) 5. 70-6.00 (1H, m), 6.61 (1H, t, J=7Hz), 6.80-7. 49 (15H, m), 7.79-8. 00 (4H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.53% | In isopropyl alcohol; at 20℃; for 0.5h; | To a solution of 6-methyl-2-pyridinecarboxaldehyde (10g, 82.55mmol) in iPrOH (200ml) were added aniline (1.2eq, 9.21g, 99mmol) and diphenylphosphite (26.85ml, 115mmol). The reaction mixture crystallised after SOmin at room temperature. iPrOH (300 ml) was added and the mixture was stirred for 2h. The resulting solid was filtered and dried to give the title compound as a white solid (40g, 99.53%); m.p. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: (4R,5R,6S)-6-[(1R)-1-trimethylsilyloxyethyl]-3-diphenylphosphoryloxy-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid pivaloyloxymethyl ester; (R)-4-mercaptopyrrolidin-2-one In acetonitrile at 5℃; for 1.16667h; Stage #2: With hydrogenchloride; water In ethyl acetate Stage #3: With sodium hydrogencarbonate In water; ethyl acetate | 3 Example 3: Production of pivaloyloxymethyl (1R, 5S, 6S)-2-[(3R)-5-oxopyrrolidin-3-yl] thio-6-[(1R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-car boxylate [] In 15 ml of acetonitrile, was dissolved 4.32 g of an oily residue containing (4R,5R,65)-6-[(1R)-1-trimethylsilyloxyethyl]-3-diphenylph osphoryloxy-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid pivaloyloxymethyl ester synthesized in the same manner as in Reference Example 2. To the resulting solution, was added 0. 57 g (4. 9 mmol) of a compound represented by formula (5): [] and was dropwise added 0.79 g (6.1 mmol) of diisopropylethylamine at 5°C, followed by stirring the mixture for 70 minutes at the same temperature. After the completion of the reaction, acetonitrile was removed by evaporation from the mixture, followed by dissolving the resulting mixture in 40 ml of ethyl acetate. The resulting solution was washed several times with aqueous sodium bicarbonate solution to remove the byproduced diphenylphosphate. To the resulting ethyl acetate solution, was added water and then aqueous 1N hydrochloric acid, until the solution has a pH of 3. The ethyl acetate solution, which was obtained by liquid separation operation, was washed with aqueous sodiumbicarbonate solution and water, and then dried over sodium sulfate. The solvent in the resulting solution was removed by evaporation, and the residue was dissolved in 20 mL of acetone. To the resulting solution, was added 30 mL of toluene. Acetone was gradually removed by evaporation from the solution, and it was observed that the resulting solution became cloudy. The cloudy solution was stirred for one hour at a temperature in the range of 0 to 5°, and the resulting solution was filtered and washed to obtain a white crystal. The crystal was dissolved in acetone again. The resulting solution was subjected to the operations of toluene addition, removal of the solvent by evaporation, stirring, filtration and washing in the same manner as described above to obtain 0. 70 g of a white crystal containing the title compound. NMRδ (CDCl3): 1.22 (9H, s), 1.27 (3H, d, J = 7.1), 1.32 (3H, d, J = 6.3 Hz), 2.39 (1H, dd, J = 5.1, 17.1 Hz), 2.83 (1H, dd, J= 8.1, 17.1 Hz), 3.26 (1H, dd, J=2.4, 6.8 Hz), 3.31-3.36 (1H, m), 3.84 (1H, dd, J = 8.1, 10.7 Hz), 4.01-4.06 (1H, m), 4.22-4.28 (2H, m), 5.82 (1H, d, J = 5.5 Hz), 5.96 (1H, d, J = 5.5 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.6% | With dmap; triethylamine In dichloromethane; acetonitrile | F.4 EXAMPLE F-4 EXAMPLE F-4 R1 =1-(triethylsilyloxy)ethyl, R2 =methyl, OR6 =OH→Cl→SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. Alcohol (a) (800 mg; 1.68 millimoles) is esterified with diphenyl chlorophosphate (0.42 ml; 1.2 equivalents), 4-(dimethylamino)pyridine (40 mg; 0.2 equivalents), and triethylamine (0.28 ml; 1.2 equivalents) in dichloromethane (10 ml) at -60° C. for 30 minutes and recovered its silyl with triethylsilyl chloride (0.75 ml; 3.9 equivalents) for 1 hour as in Example B-10 to give starting 2-chloride of (a). To a solution of this 2-chloride of (a) in acetonitrile (10 ml) are added 4-mercaptopyridine (280 mg; 1.5 equivalents) and triethylamine (0.35 ml; 1.5 equivalents). After 1 hour at -20° C., the reaction mixture is diluted with dichloromethane and poured into aqueous sodium hydrogen carbonate. The organic layer is separated, washed with aqueous ammonium chloride and water, dried (MgSO4), and concentrated in vacuum. The residue is purified by chromatography over silica gel (60 g) using toluene-ethyl acetate (1:2) to give 4-pyridyl sulfide (b) (680 mg). Yield: 71.6%. NMR (EM-390, CDCl3)δ: 0.52-0.68 (6H, m), 0.85-1.00 (9H, m), 1.15 (3H, d, J=8.7 Hz), 1.23 (3H, d, J=6 Hz), 3.18 (1H, dd, J=6.0 Hz, J=2.2 Hz), 3.09-3.30 (1H, m), 3.46, 4.91 (2H, ABq, J=14.4 Hz), 3.78 (3H s), 4.09 (1H, dd, J=13 Hz, J=2.2 Hz), 4.3-4.1 (1H, m), 5.21 (2H, s), 6.85, 7.30 (4H, ABq, J=9 Hz), 7.06, 8.30 (4H, ABq, J=6 Hz) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With 2-(Dimethylamino)pyridine; sodium iodide; triethylamine In <i>N</i>-methyl-acetamide; dichloromethane | B.10 EXAMPLE B-12 (diphenyl phosphate) EXAMPLE B-12 (diphenyl phosphate) R1 =1-(tertbutyldimethylsilyloxy)ethyl, R2 =methyl, OR6 =OPO(OPh)2 →SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. To a solution of diol (a) (4.28 g; 9.0 millimoles) and dimethylaminopyridine (550 mg; 0.3 equivalents) in dimethylformamide stirring at -70° C. is dropwise added a solution of triethylamine (2.1 ml; 1.1 equivalents) and diphenyl chlorophosphate (3.1 ml) in dichloromethane (10 ml) over 15 minutes. The mixture is stirred for 1 hour to give a solution of diphenyl phosphate (a). This product (a) is treated with 4-mercaptopyridine (1.2 equivalents), triethylamine (1.1 equivalents), sodium iodide (1.2 equivalents) and dimethylformamide (30 ml) at room temperature for 2 hours as in Example F-6 to give the corresponding 4-pyridyl sulfide (b) (4.4 g) in 85% yield. |
85% | With 2-(Dimethylamino)pyridine; sodium iodide; triethylamine In <i>N</i>-methyl-acetamide; dichloromethane | F.6 EXAMPLE F-6 EXAMPLE F-6 R1 =1-(tert-butyldimethylsilyloxy)ethyl, R2 =methyl, OR6 =OH→OPO(OPh)2 →SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. Diol (a) (4.28 g; 9.0 millimoles) is treated with dimethylaminopyridine (550 mg; 0.3 equivalents), triethylamine (2.1 ml; 1.1 equivalents), and diphenyl chlorophosphate (3.1 ml) in dimethylformamide and dichloromethane (10 ml) at -70° C. for about 1 hour as in Example B-12 to give a solution of starting diphenyl phosphate (a). To this solution of ester (a) are added 4-mercaptopyridine (1.2 equivalents), triethylamine (1.1 equivalents), sodium iodide (1.2 equivalents) and dimethylformamide. The mixture is warmed to room temperature, stirred for 2 hours, and poured into aqueous sodium hydrogen carbonate-ethyl acetate. The organic layer is separated, washed with water, dried, and concentrated in vacuum. The residue is purified by chromatography over silica gel (Lober B, ethyl acetate) to give 4-pyridyl sulfide (b) (4.4 g). Yield: 85%. |
71.6% | With dmap; chloro-trimethyl-silane; triethylamine In dichloromethane; acetonitrile | B.10 EXAMPLE B-10 (chloro) EXAMPLE B-10 (chloro) R1 =1-(triethylsilyloxy)ethyl, R2 =methyl, OR6 =Cl→SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. To a solution of alcohol (a) (800 mg; 1.68 millimoles) in dichloromethane (10 ml) at -60° C. with stirring are dropwise added 4-(dimethylamino)pyridine (40 mg; 0.2 equivalents), triethylamine (0.28 ml; 1.2 equivalents), and diphenyl chlorophosphate (0.42 ml; 1.2 equivalents). After 30 minutes' stirring, the mixture is treated with trimethylsilyl chloride (0.75 ml; 3.9 equivalents) and stirred for 1 hour to give a chloride of (a, R6 =H). This chloride (a) is treated with 4-mercaptopyridine (280 mg; 1.5 equivalents) and triethylamine (0.35 ml; 1.5 equivalents) in acetonitrile (10 ml) for 1 hour at -20° C. as in Example F-4 to give 4-pyridyl sulfide (b) (680 mg). Yield: 71.6%. |
33.7% | With 2-(Dimethylamino)pyridine; sodium iodide; triethylamine In <i>N</i>-methyl-acetamide; dichloromethane | B.10 EXAMPLE B-11 (diphenyl phosphate) EXAMPLE B-11 (diphenyl phosphate) R1 =1-hydroxyethyl, R2 =methyl, OR6 =OPO(OPh)2 →SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. To a solution of diol (a) 5.42 g (15.0 millimoles) and dimethylaminopyridine (550 mg; 0.3 equivalents) in dichloromethane (20 ml) stirring at -70° C. is dropwise added a solution of triethylamine (2.1 ml; 1.1 equivalents) and diphenyl chlorophosphate (3.1 ml) in dichloromethane (10 ml) over 15 minutes. The mixture is stirred for 1 hour to give a solution of diphenyl phosphate (a). This product (a) is treated with 4-mercaptopyridine (2.00 g; 1.2 equivalents), triethylamine (2.1 ml; 1.1 equivalents), sodium iodide (2.7 g; 1.2 equivalents), and dimethylformamide (30 ml) at room temperature for 2 hours as in Example F-5 to give 4-pyridyl sulfide (b) (2.30 g). Yield: 33.7%. IR (CHCl3)ν: 3370-3130br, 1766, 1708, 1614, 1580 cm-1. |
33.7% | With 2-(Dimethylamino)pyridine; sodium iodide; triethylamine In <i>N</i>-methyl-acetamide; dichloromethane | F.5 EXAMPLE F-5 EXAMPLE F-5 R1 =1-hydroxyethyl, R2 =methyl, OR6 =OH→OPO(OPh)2 →SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. Diol (a) (5.42 g; 15.0 millimoles) in dichloromethane (30 ml) is treated with dimethylaminopyridine (550 mg; 0.3 equivalents), diphenyl chlorophosphate (3.1 ml), and triethylamine (2.1 ml; 1.1 equivalents) for 75 minutes at -70° C. as in Example B-11 to give a solution of starting diphenyl phosphate (a). This solution is mixed with 4-mercaptopyridine (2.00 g; 1.2 equivalents), triethylamine (2.1 ml; 1.1 equivalents), sodium iodide (2.7 g; 1.2 equivalents), and dimethylformamide (30 ml), warmed up to room temperature, and stirred for 2 hours. The mixture is poured onto aqueous sodium hydrogen carbonate-ethyl acetate. The organic layer is separated, washed with water, dried, and concentrated in vacuum. The residue is chromatographed over Lober B eluding with ethyl acetate to give 4-pyridyl sulfide (b) (2.30 g). Yield: 33.7%. IR (CHCl3)ν: 3370-3130br, 1766, 1708, 1614, 1580 cm-1. NMR (VXR-200, CDCl3)δ: 1.18 (3H, d, J=7.2 Hz), 1.32 (3H, d, J=6.4 Hz), 1.76 (>1H, brs), 3.25 (1H, dd, J=6.5 Hz), J=3.0 Hz), 3.30-3.39 (1H, m), 3.48 (1H, ABq, J=14.4 Hz), 3.80 (3H, s), 4.13 (1H, dd, J=10.2 Hz, J=3 Hz), 4.22 (1H, t-type, J=6.3 Hz), 4.94 (1H, ABq, J=14.4 Hz), 5.22, 5.28 (2H, d, J=11.8 Hz), 6.88, 7.39 (4H, A2 B2 q, J=8.8 Hz), 7.06, 8.31 (4H, dA2 B2 q, J=4.6 J=1.6 Hz) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With ammonium chloride; iodine; magnesium In tetrahydrofuran; hexane; ethyl acetate | c (R)-2-(3,4-dimethoxybenzoyl)-1-trifluoroacetylpyrrolidine Step (c) (R)-2-(3,4-dimethoxybenzoyl)-1-trifluoroacetylpyrrolidine To a 250 mL round-bottom flask was added magnesium turnings (4.51 g, 0.186 mol) and 100 mL dry THF. Iodine (one crystal) was added, followed by 4-bromoveratrole (27 g, 0.124 mol) dropwise. The reaction was heated under reflux after addition of the first few drops of 4-bromoveratrole until the iodine color disappeared. Following this, the remainder of the 4-bromoveratrole was added dropwise. A condition of reflux was maintained for 2 hours. The solution was then cooled to room temperature and added to a solution of (R)-1-trifluoroacetylproline anhydride with diphenylphosphoric acid (54 g, 0.123 mol) in 250 mL dry THF at -70° C. The rate of addition was monitored to keep the reaction temperature below -60° C. Once addition was complete, the reaction mixture was warmed to room temperature and allowed to stir for 14 hours. It was then poured into a saturated aqueous solution of ammonium chloride (500 mL) and shaken. The organic layer was separated, dried with MgSO 4, and filtered, and the solvent removed in vacuo to give an oil. This oil was subjected to flash chromatography in 1:1 hexane:ethyl acetate to give 20.4 g of (R)-2-(3,4-dimethoxybenzoyl)-1-trifluoroacetyl-pyrrolidine (50% yield), m.p. 121°-123° C., [α]D25 =65° (c=1.2, CHCl3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium In xylene at 30 - 128℃; for 0.5h; | 9 Example 9; This example illustrates the extension of the process of this invention to produce phosphate forms of organoalkoxysilanes. To a 250 ml 3-neck round bottom flask fitted with a reflux condenser, thermocouple, and magnetic stir bar was charged 47.49 grams of xylene, 20.52 grams (82.0 mmole) of diphenyl phosphate, and 1.78 grams (77.4 mmole) of metallic sodium. The reaction was very slowly warmed. When the reaction mass reached approximately 30° C. it became difficult to stir. At this point 36.36 additional grams of xylene was added to help thin the reaction mass. At approximately 70° C. the diphenyl phosphate melts and becomes miscible in the xylenes. Between 90-100° C. the sodium melts and the reaction exotherms to 128° C. The reaction mass was cooled and held at 110° C. for 30 minutes and then cooled to room temperature. The resultant white solids were filtered through a 5 micron filter pad and washed twice with a total of 32.75 grams of xylene and blown dry. A total of 20.30 grams of dry solids were recovered (96% of theoretical). To a 50 ml round bottom flask was added 6.35 grams (23.3 mmole) of the sodium diphenyl phosphate whose preparation is described above. To this was added 1.05 grams of a 34.5% aqueous solution of hexaethylguanidinium chloride (0.362 grams or 1.4 mmole of hexaethylguanidinium chloride). The water was removed in vacuo. To a 250 ml 4-neck roundbottom flask fitted with a reflux condenser, thermocouple, and a magnetic stir bar was charged 6.64 grams of the dried mixture of sodium diphenyl phosphate and hexaethylguanidinium chloride described above (contains 6.28 grams or 23.1 mmole of sodium diphenyl phosphate and 0.36 grams or 1.4 mrnmole of hexaethylguanidinium chloride) and 38.36 grams (194 mmole) of 3-chloropropyltrimethoxysilane. The pot contents were heated to 120° C. and held at this temperature for 6 hours. After this time the reaction was cooled to room temperature. Gas chromatographic analysis of the crude reaction product found 20.6% of the (propyltrimethoxysilyl ester of diphenyl phosphate (93.9% of theory). The structure of the product was confirmed by GC/MS. | |
With sodium hydroxide In methanol at 20℃; for 2h; | ||
With sodium hydrogencarbonate In water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With CCl4 In dichloromethane byproducts: CH3CO2H; addn. of HO2P(OPh)2 soln. to soln of Fe-complex, stirring for 1 h, evapn., dissolution in CCl4, standing for 3 days, pptn.; filtration, washing (CCl4, hexanes), powdering, drying (vacuum); elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With triethylamine In ethanol filtration after 1 h; pptn. with diethyl ether, recrystn. (methanol-acetone); | |
19% | With triethylamine In ethanol reaction for several days; elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: C18H18O3; diphenyl phosphoryl azide With triethylamine In toluene at 80℃; for 2.5h; Stage #2: With sodium hydroxide; water In tetrahydrofuran at 20℃; for 1h; | 30 The acid obtained above was suspended in anhydrous toluene (1.5 ml). TEA (84 ul, 2 equiv.) and DPPA (130 ul, 2 equiv.) were added. The contents were shaken at 8O0C for 2.5 hours. The reaction mixture was cooled to room temperature and concentrated. The residue was dissolved in THF (3 ml). 2 M NaOH (1.5 ml) was added. The contents were stirred at room temperature for 1 hour. 2 M NaOH (1 ml) was added. The mixture was extracted with EtOAc (3 X 2.5 ml). The combined organic layer was dried over Na2S O4 and concentrated in ~ 2 ml in volume. It was flashed through a Biotage 40 S silica column with EtOAc/MeOH (95:5) to afford the desired product (97.3 mg, still contaminated with some (PhO)2POOH). 1 H-NMR (400 MHz1 CD3OD): δ = 7.37-7.43 (m, 4 H), 7.18-7.25 (m, 4 H), 7.04 (t, 1 H), 4.07 (dd, 1 H)1 4.01 (dd, 1 H), 3.52 (dt, 1 H), 3.23 (t, 1 H), 3.13 (dt, 1 H), 2.62 (dt, 1 H)1 1.90-1.95 (m, 1 H), 1.805 (dd, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With [bis(acetoxy)iodo]benzene In acetonitrile at 20℃; for 1h; | |
71% | With ammonium iodide; 3-chloro-benzenecarboperoxoic acid In acetonitrile at 20℃; for 8h; | NH4I catalytic phosphoryloxylactonisation of alkenoic acids; typicalprocedure To CH3CN (5 mL), pent-4-enoic acid (0.030 g, 0.3 mmol), diphenylphosphate (0.090 g, 0.36 mmol), mCPBA (75%, 0.138 g, 0.60 mmol)and NH4I (0.0043 g, 0.030 mmol) were added. The mixture wasstirred at room temperature for 8 h. Then H2O (5 mL), sat.aq Na2S2O3(2 mL) and sat. aq Na2CO3 (2 mL) were added. The mixture wasextracted with CH2Cl2 (3 × 5 mL) and the combined organic extractwas dried over anhydrous Na2SO4, filtered, and concentrated underreduced pressure. The residue was purified on silica gel plate using(3 : 2 hexane-ethyl acetate) as eluent to afford 5-(bis(phenyloxy)phosphoryl)oxy-4-pentanolactone in 71% yield. |
65% | With iodobenzene; 3-chloro-benzenecarboperoxoic acid; trifluoroacetic acid at 20℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With ammonium iodide; 3-chloro-benzenecarboperoxoic acid In acetonitrile at 20℃; for 8h; Optical yield = 58.333 %de; | NH4I catalytic phosphoryloxylactonisation of alkenoic acids; typical procedure General procedure: To CH3CN (5 mL), pent-4-enoic acid (0.030 g, 0.3 mmol), diphenylphosphate (0.090 g, 0.36 mmol), mCPBA (75%, 0.138 g, 0.60 mmol)and NH4I (0.0043 g, 0.030 mmol) were added. The mixture wasstirred at room temperature for 8 h. Then H2O (5 mL), sat.aq Na2S2O3(2 mL) and sat. aq Na2CO3 (2 mL) were added. The mixture wasextracted with CH2Cl2 (3 × 5 mL) and the combined organic extractwas dried over anhydrous Na2SO4, filtered, and concentrated underreduced pressure. The residue was purified on silica gel plate using(3 : 2 hexane-ethyl acetate) as eluent to afford 5-(bis(phenyloxy)phosphoryl)oxy-4-pentanolactone in 71% yield. |
63% | With iodobenzene; 3-chloro-benzenecarboperoxoic acid; trifluoroacetic acid at 20℃; for 8h; | |
With [bis(acetoxy)iodo]benzene In acetonitrile at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With iodobenzene; 3-chloro-benzenecarboperoxoic acid; trifluoroacetic acid at 20℃; for 8h; | |
63% | With ammonium iodide; 3-chloro-benzenecarboperoxoic acid In acetonitrile at 20℃; for 8h; | NH4I catalytic phosphoryloxylactonisation of alkenoic acids; typicalprocedure General procedure: To CH3CN (5 mL), pent-4-enoic acid (0.030 g, 0.3 mmol), diphenylphosphate (0.090 g, 0.36 mmol), mCPBA (75%, 0.138 g, 0.60 mmol)and NH4I (0.0043 g, 0.030 mmol) were added. The mixture wasstirred at room temperature for 8 h. Then H2O (5 mL), sat.aq Na2S2O3(2 mL) and sat. aq Na2CO3 (2 mL) were added. The mixture wasextracted with CH2Cl2 (3 × 5 mL) and the combined organic extractwas dried over anhydrous Na2SO4, filtered, and concentrated underreduced pressure. The residue was purified on silica gel plate using(3 : 2 hexane-ethyl acetate) as eluent to afford 5-(bis(phenyloxy)phosphoryl)oxy-4-pentanolactone in 71% yield. |
With [bis(acetoxy)iodo]benzene In acetonitrile at 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With ammonium iodide; 3-chloro-benzenecarboperoxoic acid; In acetonitrile; at 20℃; for 8h; | General procedure: To CH3CN (5 mL), pent-4-enoic acid (0.030 g, 0.3 mmol), diphenylphosphate (0.090 g, 0.36 mmol), mCPBA (75%, 0.138 g, 0.60 mmol)and NH4I (0.0043 g, 0.030 mmol) were added. The mixture wasstirred at room temperature for 8 h. Then H2O (5 mL), sat.aq Na2S2O3(2 mL) and sat. aq Na2CO3 (2 mL) were added. The mixture wasextracted with CH2Cl2 (3 × 5 mL) and the combined organic extractwas dried over anhydrous Na2SO4, filtered, and concentrated underreduced pressure. The residue was purified on silica gel plate using(3 : 2 hexane-ethyl acetate) as eluent to afford 5-(bis(phenyloxy)phosphoryl)oxy-4-pentanolactone in 71% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: diphenyl hydrogen phosphate; copper(II) nitrate trihydrate In methanol; water for 0.25h; Stage #2: [2,2]bipyridinyl In methanol; water for 3h; | Syntheses of the complexes General procedure: An aqueous solution of copper(II) nitrate trihydrate (1 mmol, 0.241 g) was mixed with a methanolic solution (10 ml) of diphenyl phosphate (1 mmol, 0.250 g) with constant stirring for 15 min. After that, a methanolic solution (10 ml) of 1,10-phenanthroline (1 mmol, 0.198 g) was added to the above mixture. After stirring the mixture for 3 h, it was filtered and the filtrate was kept in a CaCl2-desiccator. Deep blue single crystals suitable for X-ray diffraction analysis were obtained after 14 days (yield 78%). Anal. Calc. for C48H36N6 O14P2 Cu2: C, 51.94; H, 3.26; N, 7.57. Found: C, 51.92; H, 3.25; N, 7.54%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: diphenyl hydrogen phosphate; copper(II) nitrate trihydrate In methanol; water for 0.25h; Stage #2: 1,10-Phenanthroline In methanol; water for 3h; | Syntheses of the complexes General procedure: An aqueous solution of copper(II) nitrate trihydrate (1 mmol, 0.241 g) was mixed with a methanolic solution (10 ml) of diphenyl phosphate (1 mmol, 0.250 g) with constant stirring for 15 min. After that, a methanolic solution (10 ml) of 1,10-phenanthroline (1 mmol, 0.198 g) was added to the above mixture. After stirring the mixture for 3 h, it was filtered and the filtrate was kept in a CaCl2-desiccator. Deep blue single crystals suitable for X-ray diffraction analysis were obtained after 14 days (yield 78%). Anal. Calc. for C48H36N6 O14P2 Cu2: C, 51.94; H, 3.26; N, 7.57. Found: C, 51.92; H, 3.25; N, 7.54%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In methanol at 20℃; for 0.166667h; | 4.5 Synthesis of [Mn(dpp)(bpy)2]2(ClO4)2 (4) To the methanolic solution of [Mn(OAc)(bpy)2](ClO4)(H2O) (543 mg, 1 mmol in 40 mL), dpp-H (250 mg, 1 mmol) was added and stirred for 10 min. The resultant solution was filtered and the filtrate was crystallized at room temperature to obtain X-ray diffraction quality crystals. Yield: 0.60 g (84%). Mp: 267-270°C. Anal. Calc. for C64H52Cl2Mn2N8O16P2 (Mr=1431.9): C, 53.68; H, 3.66; N, 7.83. Found: C, 53.3; H, 3.5; N, 7.5%. IR (KBr, cm-1): 3070 (w), 1595 (m), 1576 (w), 1489 (m), 1474 (w), 1440 (s), 1315 (w), 1288 (w), 1268 (s), 1257 (m), 1202 (m), 1159 (w), 1107 (vs), 1015 (m), 935 (m), 894 (w), 756 (s), 738 (w), 692 (w), 648 (w), 623 (m). UV-Vis (CH3OH, nm, ε, cm-1M-1): 97 (19090). Fluorescence: (λex=297 nm, CH3OH): 325, nm. TGA: Temp. range °C (% weight loss): 215-289 (10.4); 290-372 (50.8); 373-897 (18.2). DSC (°C): 226 (endo); 351 (exo). μfound=9.72 BM. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium hydroxide In water for 4h; | 2.2 General procedure for the synthesis of neodymium tris-diarylphosphates 16-28 General procedure: A solution of KOH (0.35 g, 6.2 mmol) in water (5 mL) was addedto a suspension of finely ground phosphoric acid ester (6.2 mmol)in water (20 mL). Water (40 mL) and neodymium nitrate (0.88 g,2 mmol) in water (30 mL) were added to the resulting solution withstirring. After 4 h of stirring, the mixture was filtered and washedwith 4 mL × 40 mL of water. The white precipitate was dried in avacuum desiccator twice over CaCl2and once over P2O5to a con-stant mass (the precipitate turned light blue). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With 1-Butylimidazole; phosphoric acid; triethylamine In N,N-dimethyl-formamide at 230℃; for 24h; Inert atmosphere; | General procedure for the synthesis of diaryl phosphates General procedure: Phosphoric acid 85% (461.2 mg, 4.0 mmol), phenol (3.76 g, 40 mmol), triethylamine (1.21 g, 12 mmol), 1-butylimidazole (149.0 mg, 1.2 mmol) and DMF (5 mL) were placed in the reaction apparatus consisted of a 50 mL three-necked flask with a tube through which the boiling solvent and water vapor flowed and a tube through which the solvent was refluxed through the dehydrating agent. (See Fig. S1) PAdeCS, 2.0 gram as a drying agent is put under the condenser. The reaction was heated at 230 °C for 24 h and after this time, the resulting mixture was run through cation exchange resin (eluent: MeOH) to remove amines. After evaporation of eluent, the mixture was distilled at low pressure to remove phenol and DMF. The desired diphenyl hydrogen phosphate is obtained by gel permeation chromatography GPC (eluent: CHCl3), 71% (619.6 mg, 2.84 mmol). |
71% | With 1-Butylimidazole; phosphoric acid; triethylamine In N,N-dimethyl-formamide at 230℃; for 24h; Inert atmosphere; | General procedure for the synthesis of diaryl phosphates General procedure: Phosphoric acid 85% (461.2 mg, 4.0 mmol), phenol (3.76 g, 40 mmol), triethylamine (1.21 g, 12 mmol), 1-butylimidazole (149.0 mg, 1.2 mmol) and DMF (5 mL) were placed in the reaction apparatus consisted of a 50 mL three-necked flask with a tube through which the boiling solvent and water vapor flowed and a tube through which the solvent was refluxed through the dehydrating agent. (See Fig. S1) PAdeCS, 2.0 gram as a drying agent is put under the condenser. The reaction was heated at 230 °C for 24 h and after this time, the resulting mixture was run through cation exchange resin (eluent: MeOH) to remove amines. After evaporation of eluent, the mixture was distilled at low pressure to remove phenol and DMF. The desired diphenyl hydrogen phosphate is obtained by gel permeation chromatography GPC (eluent: CHCl3), 71% (619.6 mg, 2.84 mmol). |
Multi-step reaction with 2 steps 1: trichlorophosphate; pyridine / benzene / 5 h / Reflux 2: lithium hydroxide monohydrate / propan-2-one / 1 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With caesium carbonate In acetonitrile at 100℃; for 12h; Inert atmosphere; | 19 General procedure General procedure: To a mixture of P(O)-OH compounds (0.5 mmol) and Cs2CO3 (1.0 mmol) in CH3CN (3 mL), alkyl halide (0.5 mmol) was added under nitrogen atmosphere; the resulting mixture was stirred at 100 °C for 12 h. Removal of the solvent under a reduced pressure gave the crude product; pure product was obtained by passing the crude product through a short silica gel column using Hexane/EtOAc as eluant. 4.2.19. Benzyl diphenyl phosphate (4e) 12l Yield: 120.8 mg, (71%). Colorless oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ=7.29-7.36 (m, 10H; Ar), 7.17-7.25 (m, 5H; Ar), 5.25 (d, J=8.8 Hz, 2H; -OCH2); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ=150.5 (d, 1J (C,P)=7.1 Hz; Ar), 129.8 (s; Ar), 128.8 (s; Ar), 128.6 (s; Ar), 128.1 (s; Ar), 127.8 (d, 1J (C,P)=10.6 Hz; Ar), 125.4 (s; Ar), 120.1 (d, 1J (C,P)=4.8 Hz; Ar), 70.6 (d, 1J (C,P)=5.9 Hz; -OCH2); 31P NMR (160 MHz, CDCl3, 25 °C): δ=-11.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With copper(l) iodide; sodium carbonate; triethylamine In tetrachloromethane at 80℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triethylamine In toluene at 110℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With tetrachloromethane; copper; sodium carbonate; triethylamine; In dichloromethane; at 100℃; for 12h;Sealed tube; | General procedure: A mixture of P(O)-OH compounds (0.5 mmol), Na2CO3(1 mmol), CCl4 (2 mmol), Et3N (0.5 mmol) and Cu powder(0.25 mmol) in CH2Cl2 (3 mL) was stirred at 100 C under air atmospherefor 12 h. Removal of the solvent under reduced pressure gave the crude product; pure product was obtained by passing the crude product through a short silica gel column using Hexane/EtOAc (1:1 to 5:1) as eluent. |
27% | With dicyclohexyl-carbodiimide; In 1,4-dioxane; at 20℃; for 6h;Inert atmosphere; | General procedure: A mixture of P(O)OH compounds (0.5 mmol), alcohol (0.5 mmol), and DCC (0.55 mmol) was dissolved in dioxane under N2 atmosphere, stirred at room temperature for 6h. Removal of the solvent under a reduced pressure gave the crude product; pure product was obtained by passing the crude product through a short silica gel column using Hexane/EtOAc (1:1-5:1) as eluent. |
11% | With N,N-dimethyl-aniline; 1,1'-carbonyldiimidazole; In acetonitrile; at 20℃; for 12h;Inert atmosphere; | General procedure: A mixture of P(O)-OH compounds (0.5mmol), phenols (0.5mmol), CDI (0.5mmol) and PhNMe2 (0.75mmol) in CH3CN (1.0mL) was stirred at room temperature under N2 atmosphere for 12h. Removal of the solvent under reduced pressure gave the crude product; pure product was obtained by passing the crude product through a short silica gel column using Hexane/EtOAc (1:1-5:1) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; diastereoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; diastereoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; diastereoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; diastereoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; chemoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 69% 2: 15% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; diastereoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; diastereoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; regioselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; regioselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; diastereoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; chemoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; diastereoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; diastereoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With N-Bromosuccinimide at 25℃; for 24h; Inert atmosphere; chemoselective reaction; | General procedure General procedure: Phosphate 2a-2e (0.101 mmol, 1.01 equiv) was added to the solution of olefin 1a-1k (0.10 mmol, 1 equiv) and NXS (0.20 mmol, 2 equiv) in respective cyclic ether (3 mL). The reaction mixture was stirred for 24 at room temperature. The solvent was then removed under reduce pressure and residue was purified by flash column chromatography (gradient elution, EtoOAc: n-hexane; 1:100 v/v, 50 mL; 1:20, v/v 400 mL), to yield the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N-Bromosuccinimide at 25℃; for 12h; | 69 Example 69 Cyclohexene (8.2mg, 0.1mmol), NBS (53.1mg, 0.3mmol, 3Equiv.) Was dissolved in 4mLTHF added diphenyl phosphate (25mg, 0.101mmol, 1.01Equiv.), 25 reaction 12h, decompression The solvent was removed, the residue was purified by silica gel column chromatography (EtOAc: n-hexane; 1: 100V / V, 50mL; 1: 20, V / V400mL), to give a colorless oily liquid 45.7 mg, 95% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With N-Bromosuccinimide at 65℃; for 12h; | 68 Example 68 4- (2-bromocycloheptyloxy) butyldiphenylphosphate Cycloheptene (9.6mg, 0.1mmol), NBS (53.1mg, 0.3mmol, 0.3Equiv.) Was dissolved in 5mLTHF added diphenyl phosphate (25mg, 0.101mmol, 1.01Equiv.), 65 reaction 12h, Save The solvent was removed pressure, the residue was purified by silica gel column chromatography (EtOAc: n-hexane; 1: 100V / V, 50mL; 1: 20, V / V400mL), to give 36.7 mg of the colorless, oily liquid, yield 74%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74.8% | With N-Bromosuccinimide at 25℃; for 30h; Inert atmosphere; | 6 Example 6 The substrate usedIsDiphenyl phosphate (52.5mg, 0.21mmol, 1.01Equiv.), N- bromosuccinimide was added, reacted at 25 deg.] C, other experimental methods and conditions as in Example 1, to obtain a colorless oily liquid 90.9 mg, yield 74.8%.TwoNon enantiomers determined by HPLC The chalcone (41.6mg, 0.2mmol) and (R / S) -1,1'- binaphthyl-2,2'-diyl hydrogen phosphate (73.1mg, 0.21mmol, 1.01Equiv.) Was dissolved in 2mLTHF ; and at room temperature, under argon atmosphere, was slowly every 2hWas added N- bromosuccinimide (0.1mmol, 0.5Equiv.) For a total of 4 times was added, N- bromosuccinimide was added, reaction was continued for 24h, the solvent was removed under reduced pressure, the residue by column chromatography gel (ethyl acetate: n-hexane; (1: 10, V / V, 100mL), (1: 5, V / V100mL), (1: 3, V / V, 200mL)), to give a colorless oily liquid121.7mg, yield 86%.The product form two diastereomers by high performance liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With N-Bromosuccinimide at 35℃; for 12h; | 55 Example 55 (E) - diphenylethylene (18mg, 0.1mmol), NBS (. 44.5mg, 2.5Equiv) was dissolved 2mLTHF added diphenyl phosphate (25.2mg, 0.101mmol, 1.01Equiv.), 35 reaction 12h, the solvent was removed under reduced pressure, the residue was purified by silica gel column chromatography (EtOAc: n-hexane; 1: 100V / V, 50mL; 1: 20, V / V400mL), to give a colorless oily liquid 56.2 mg, yield 97% . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With oxygen; urea; copper(I) bromide; In acetonitrile; at 80℃; for 12h;Molecular sieve; Schlenk technique; | 248mg (1.0mmol) phosphoric acid diphenyl ester, 122mg (1.0mmol) phenylboronic acid, 120mg (2.0mmol) urea, 100mg molecular sieve, and 28.7mg (0.2mmol) cuprous bromide under oxygen atmosphere were added in a Schlenk tube. Under oxygen atmosphere, 3.0ml acetonitrile was added. The reaction was stirred at 80C for 12 hours. After completion of the reaction, it was separated and purified to obtain 65% yield of O-triphenyl phosphate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With deuteromethanol In dichloromethane at 20℃; for 48h; | |
With d(4)-methanol In dichloromethane at 20℃; for 48h; | ||
With d(4)-methanol for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.6% | With dmap; In dichloromethane; at 20℃; for 12h; | Under argon protection and ice bath conditions, the solid (1)-Brefeldin A 280 mg (l. Ommol) was added to a solution containing 3. Ommol of diphenylhydrophosphite and 0. 2 mmol of 4-dimethylamino- DMAP in 10 mL of anhydrous methylene chloride solution, 0.5h plus, the ice bath to continue stirring for 2h, the natural temperature to room temperature The mixture was further stirred for 12 h, and then 6 mmol of isopropyl alcohol (transesterification reagent) was added to the reaction solution at room temperature and allowed to proceed at room temperature The reaction was stirred for 12 h, concentrated under reduced pressure, separated by silica gel column chromatography, [V (CH2C12): V (CH30H) = 60: 1] to give the target product <strong>[20350-15-6](+)-Brefeldin A</strong>-4,7-0-dihydro-phosphite isopropyl ester was added 218 mg of colorless viscous oil in 88.6% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap In dichloromethane at 20℃; for 16h; | 5 A dry 50 mL round bottom flask was charged with (+)-Brefeldin A-7-O-t-butyldimethylsilane (3a) 394 mg (lmmol), DMAP 12 mg (0.1 l mmol), followed by addition of 20 mL of dry dichloromethane, ° C. Stirring slowly through the constant pressure dropping funnel slowly dropping 1.2mmol of diphenyl hydrogen phosphite, lOmin drops finished. Rose to room temperature The reaction was continued for 16 h and then isopropanol (4 mmol) (transesterification reagent) was added to the reaction solution at room temperature and the mixture was stirred at room temperature Mixing reaction 12h, the reaction is complete. The solvent was removed by distillation under reduced pressure and treated with petroleum ether: ethyl acetate = 4: 1 as eluent, silica gel column Chromatography to give colorless transparent liquid 4-0-isopropyl hydrogen phosphite-7-O-tert-butyldimethyl- (+) -Brefeldin A446 mg, yield 89.2% (Figure 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: picoline; copper(II) perchlorate hexahydrate In methanol; water for 0.5h; Stage #2: diphenyl hydrogen phosphate In methanol; water for 4h; | 2.3a Synthesis of [Cu(dpp)(pmdeta)].ClO4.H2O}2(1) General procedure: 1 mmol of Cu(ClO4)2.6H2O (i.e., 0.3704 gm) was dissolved in 10mL water in a 50mL flat bottom flask. Then 1 mmol (i.e., 0.21 mL) of pentamethyldiethylenetriamine (pmdeta) was dissolved in 10mL MeOH in a beaker. This solution was added to the flat-bottom flask. After that the above mixture was stirred for 30 min when a deep blue color appeared. Then 1 mmol (i.e., 0.250 gm) aqueous solution of diphenyl phosphate (dpp) was added to the deep blue solution and the resultant mixture was stirred for 4 h. The resulting blue solution was filtered and filtrate was kept in desk. After seven days block shaped blue crystals suitable for X-ray diffraction analysis were obtained in the reaction beaker. The crystals were separated and washed with methanol-water (1:1) mixture and dried under air (Yield: 60%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With (2R,2'R)-2,2'-([2-iodo-1,3-phenylene]bis(oxy))bis(N-mesitylpropanamide); 3-chloro-benzenecarboperoxoic acid In diethyl ether; 2,2,2-trifluoroethanol at -45 - 20℃; for 120h; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With (2R,2'R)-2,2'-([2-iodo-1,3-phenylene]bis(oxy))bis(N-mesitylpropanamide); 3-chloro-benzenecarboperoxoic acid In diethyl ether; 2,2,2-trifluoroethanol at 0℃; for 72h; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With (2R,2'R)-2,2'-([2-iodo-1,3-phenylene]bis(oxy))bis(N-mesitylpropanamide); 3-chloro-benzenecarboperoxoic acid In diethyl ether; 2,2,2-trifluoroethanol at -45 - 20℃; for 120h; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With (2R,2'R)-2,2'-([2-iodo-1,3-phenylene]bis(oxy))bis(N-mesitylpropanamide); 3-chloro-benzenecarboperoxoic acid In diethyl ether; 2,2,2-trifluoroethanol at 0℃; for 72h; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: diphenyl hydrogen phosphate; sodium hydroxide In methanol at 20℃; for 2h; Stage #2: N<SUP>1</SUP>,N<SUP>3</SUP>-bis(3-methoxysalicylidene)diethylenetriamine; erbium(III) chloride hexahydrate With triethylamine In methanol | [ErNa(valdien)Cl((PhO)2PO2)]n (1) To a solution of H2valdien (0.15mmol, 55mg), Et3N (0.30mmol, 41.8μL) in MeOH (3mL) was added a MeOH solution (2mL) of ErCl3·6H2O (0.15mmol, 57mg). The solution was stirred for 3min, and then a MeOH solution (2mL) of Na(PhO)2PO2 (0.15mmol, 40.5mg) was added to the mixture. The resulting clear yellow solution was stirred briefly and filtered. The yellow block crystals suitable for X-ray diffraction studies were obtained by slow diffusion of isopropyl ether vapor into the yellow solution after 3days. Yield: ca. 45%. Elemental analysis (%) calculated for C32H33ClErN3NaO8P: C, 45.52; H, 3.94; N, 4.98. Found: C, 45.48; H, 3.99; N, 4.96. IR (KBr, cm-1): 3439 (m), 3203 (w), 2918 (w), 1628 (vs), 1602 (w), 1489 (w), 1471 (s), 1455 (s), 1440 (w), 1252 (vs), 1220 (s), 1099 (s), 1079 (m), 923 (m), 910 (s), 901 (m), 899 (m), 750 (m), 742 (s), 626 (w), 534 (m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In water at 85℃; for 4h; | 8 Example 8 At room temperature, 25.0 g (0.1 mol) of diphenyl phosphate was added to 100 ml of water, and while stirring, 12.6 g(0.1mol) melamine to mix well, then heated to 85 reaction 4h, cooled to room temperature, filtered to remove the water was whiteSolid, drying, is the final product. Yield 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In ethanol at 72℃; | 6 Example 6 At room temperature, 25.0 g (0.1 mol) of diphenyl phosphate was added to 100 ml of ethanol, and while stirring, 12.8 g(0.1 mol) 2-amino-4,6-dihydroxy s-triazine to mix well, then heated to 72 reaction 3h, cooled to room temperatureEthanol was removed by filtration to give a white solid, dried, that is, the final product. Yield 98%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In ethanol at 70℃; for 4h; | 7 Example 7 At room temperature, 25.0 g (0.1 mol) of diphenyl phosphate was added to 100 ml of ethanol, and while stirring, 12.7 g(0.1mol) 4,6-diamino-2-hydroxy-1,3,5-triazine to mix well, then heated to 70 reaction 4h, cooled to roomTemperature, ethanol was removed by filtration to give a white solid, drying, that is, the final product. Yield 98%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: diphenyl hydrogen phosphate; methyl (S)-2-amino-4-(3-((tert-butoxycarbonyl)amino)piperidin-1-yl)-5-fluorobenzoate; 3-hydroxy-2-butanon In Isopropyl acetate at 70 - 75℃; for 30h; Stage #2: With water In Isopropyl acetate at 70℃; for 24h; | 1.2 Step 2: Preparation of Methyl (S)-4-(3-aminopiperidin-l-yl)-5-fluoro-2,3-dimethyl-lH- indole-7-carboxylate To a reactor were charged methyl (S)-2-amino-4-(3-((tert-butoxycarbonyl)amino) piperidin-l-yl)-5-fluorobenzoate (5.0 g), DPPOH (diphenyl phosphate, 6.81 g, 2 eq) and 3-hydroxybutanone (1.2 eq, 1.44 g), followed by addition of isopropyl acetate (100 mL, 20 mL/g). The mixture was allowed to warm up to 70 to 75 °C, resulting in a yellow solution. The solution was stirred at 70 to 75 °C for 30 h to complete the cyclization. (0225) Water (2 mL) was added and the mixture was aged at 70 °C over 24 h to remove the Boc group. The mixture was cooled to room temperature. Next, aqueous 20% K3PO4 solution (50 mL) was added and the mixture was stirred for 15 min. The organic layer was separated and washed with water (50 mL). The organic layer was then concentrated under vacuum (200 Torr) to -50 mL. The resulting slurry was stirred at 50 °C for 2 h and then heptane (100 mL) was added over 1 h. The mixture was cooled to room (0226) temperature, stirred for 20 h, and then filtered. The cake was washed with heptane (50 mL). Methyl (S)-4-(3-aminopiperidin-l-yl)-5-fluoro-2,3-dimethyl-lH-indole-7- carboxylate, DPPOH salt was obtained as a light yellow solid. The wet-cake was added to a reactor. Isopropyl acetate (100 mL) was added, followed by addition of aqueous K3PO4 solution (4 g in water 50 mL). The mixture was stirred at room temperature for -half-hour, resulting in a two phase clear solution (pH >10 for aqueous). The organic layer was separated and washed with water (50 mL), and then concentrated under vacuum to a volume of 15 mL. The resulting slurry was stirred at room temperature for 4 h, then heptane (75 mL) was added over 1 h. The mixture was aged at room temperature for 24 h, then concentrated to a volume to -50 mL. The slurry was filtered. The cake was washed with heptane 20 mL and dried under vacuum at 50 °C for 24 h. Methyl (S)-4-(3- aminopiperidin-l-yl)-5-fluoro-2,3-dimethyl-lH-indole-7-carboxylate was obtained as a light yellow solid (2.76 g, yield: 69%). NMR (400MHz, DMSO-d6) δ 10.64 (s, 1H), 7.33 (d, J=13.7 Hz, 1H), 3.89 (s, 3H), 3.14 (br. m., 1H), 3.07-2.90 (m, 2H), 2.84 (br. m., 1H), 2.70 (br. m., 1H), 2.35 (s, 3H), 2.33 (s, 3H), 1.87 (br. m., 1H), 1.67 (br. m., 3H). LC-MS: M+H= 320. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With N-iodo-succinimide In tetrahydrofuran at 40℃; for 12h; Inert atmosphere; | 22 Example 22 Preparation of diphenyl (2-iodo-1-phenylethyl) phosphate 0.5 mmol of diphenoxyphosphinic acid,0.5 mmol of styrene and 0.6 mmol of N-iodosuccinimide were added to the Schlenk tube under nitrogen.Add 1.0 mL of tetrahydrofuran under a nitrogen atmosphere and stir the reaction at 40 oC for 12 hours.After the reaction is completed, the target product can be obtained in 69% yield by column chromatography. |
69% | With N-iodo-succinimide In tetrahydrofuran at 40℃; for 6h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | at 110℃; for 24h; Sealed tube; | General procedure for the synthesis of phosphonium salts 3 General procedure: As shown in Tables 1 and 2, phosphine, acid and orthoformate in a mol ratio of 1:1:5 were added to the reaction tube. The reaction mixture was stirred at 110 °C. After the completion of the reaction, the reaction mixture was cooled to room temperature, and the excessed orthoformate was evaporated under reduced pressure. The obtained residue was recrystallized with dichloromethane andethyl acetate, and washed with ethyl acetate and petroleum ether .The product was dried in a vacuum oven at 60 °C overnight to obtain desired pure phosphonium salts. |
94% | at 110℃; for 24h; Sealed tube; | 1 Example 1This embodiment is a method for synthesizing a quaternary phosphonium salt flame retardant. The specific steps are as follows: Add triphenylphosphine (0.0035mol), thenDiphenyl phosphate (0.00355mol)And trimethyl orthoformate (1.8ml),And add the stirring bar.The reaction system was sealed and reacted at 110°C for 24 hours.After the reaction, cool to room temperature,The solvent was evaporated under reduced pressure,Dichloromethane and ethyl acetate were used for recrystallization.The obtained solid was washed with ethyl acetate and petroleum ether,The white solid obtained after suction filtration was transferred to a vacuum oven at 60°C and dried overnight to obtain a solid quaternary phosphonium salt flame retardant (PFR-1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In dimethyl sulfoxide at 85℃; for 3h; | 123 Example 123Manufacturing method of phthalocyanine 123 2 parts of phthalocyanine 1, 0.6 parts of diphenyl phosphate and 40 parts of dimethyl sulfoxide were mixed.After reacting at 85 ° C. for 3 hours, the reaction solution was added to 40 parts of water.The precipitate is filtered, washed with 20 parts of water, dried, and then dried.1.7 parts of phthalocyanine 101 was obtained in a yield of 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | In toluene at 20℃; for 0.166667h; regioselective reaction; | |
94% | In toluene at 20℃; for 0.166667h; Schlenk technique; Inert atmosphere; | 2 2. Substrate type General procedure: In 15mL Schlenk, add alkynamide 1 (0.15mmol) phosphate 2 (0.18mmol), add 1.5mL toluene to dissolve, and react at room temperature for 10min. After finishing,Separate directly by column chromatography,The mobile phase is petroleum ether/ethyl acetate 4/1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In 1,4-dioxane at 80℃; for 3h; | General procedure for the preparation of product 2H-chromen-4-yl phosphinates/phosphonates 3, 4, and 5: General procedure: The mixture of 2-propynolphenols 1 (0.1 mmol) and R2P(O)OH (0.2 mmol) was stirred in DCE or 1,4-dioxane (2.0 mL) at 80°C under air. After 3.0 h, the completion of the reaction was monitored by TLC. Then, the solvent was concentrated and the residue was purified by flash chromatography on silica gel to afford the desired products. 2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In 1,4-dioxane at 80℃; for 3h; | General procedure for the preparation of product 2H-chromen-4-yl phosphinates/phosphonates 3, 4, and 5: General procedure: The mixture of 2-propynolphenols 1 (0.1 mmol) and R2P(O)OH (0.2 mmol) was stirred in DCE or 1,4-dioxane (2.0 mL) at 80°C under air. After 3.0 h, the completion of the reaction was monitored by TLC. Then, the solvent was concentrated and the residue was purified by flash chromatography on silica gel to afford the desired products. 2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | In 1,4-dioxane at 80℃; for 3h; | General procedure for the preparation of product 2H-chromen-4-yl phosphinates/phosphonates 3, 4, and 5: General procedure: The mixture of 2-propynolphenols 1 (0.1 mmol) and R2P(O)OH (0.2 mmol) was stirred in DCE or 1,4-dioxane (2.0 mL) at 80°C under air. After 3.0 h, the completion of the reaction was monitored by TLC. Then, the solvent was concentrated and the residue was purified by flash chromatography on silica gel to afford the desired products. 2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In 1,4-dioxane at 80℃; for 3h; | General procedure for the preparation of product 2H-chromen-4-yl phosphinates/phosphonates 3, 4, and 5: General procedure: The mixture of 2-propynolphenols 1 (0.1 mmol) and R2P(O)OH (0.2 mmol) was stirred in DCE or 1,4-dioxane (2.0 mL) at 80°C under air. After 3.0 h, the completion of the reaction was monitored by TLC. Then, the solvent was concentrated and the residue was purified by flash chromatography on silica gel to afford the desired products. 2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43.38% | Stage #1: diphenyl hydrogen phosphate With 1,1'-carbonyldiimidazole In tetrahydrofuran at 60℃; for 1h; Stage #2: AN2728 In tetrahydrofuran for 2h; | 7 Example 7 Synthesis of compound of formula I-7 Add 464mg of the compound of formula 2-7, 1g of N,N'-carbonyldiimidazole (CDI), 8mL of THF to the reaction flask, and after stirring and reacting at 60°C for 1h, add 400mg of the compound of formula 1 in THF (8mL) to the reaction flask , Continue the reaction for 2h, TLC monitors the reaction, and the reaction is complete. The reaction solution was cooled to room temperature, silica gel was added to mix the sample, and the target compound was separated by column chromatography (eluent EA:PE=1:3) to obtain 389 mg of white solid compound of formula I-7, yield: 43.38%. |
Tags: 838-85-7 synthesis path| 838-85-7 SDS| 838-85-7 COA| 838-85-7 purity| 838-85-7 application| 838-85-7 NMR| 838-85-7 COA| 838-85-7 structure
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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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