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Chemical Structure| 1030825-21-8 Chemical Structure| 1030825-21-8

Structure of 1030825-21-8

Chemical Structure| 1030825-21-8

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Product Details of [ 1030825-21-8 ]

CAS No. :1030825-21-8
Formula : C25H27FO6S
M.W : 474.54
SMILES Code : O[C@@H]1[C@@H](O)[C@H](O)[C@H](OC1(OC)C2=CC=C(C(CC3=CC=C(S3)C4=CC=C(C=C4)F)=C2)C)CO
MDL No. :MFCD21496493

Safety of [ 1030825-21-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P264-P270-P301+P312-P330

Application In Synthesis of [ 1030825-21-8 ]

* 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.

  • Downstream synthetic route of [ 1030825-21-8 ]

[ 1030825-21-8 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 1030825-20-7 ]
  • [ 32469-28-6 ]
  • [ 1030825-21-8 ]
YieldReaction ConditionsOperation in experiment
93.7% This embodiment is a method for preparing a cardinol intermediate, and the preparation method comprises the following steps:1) Under the protection of nitrogen,100 g (0.245 mol) of <strong>[1030825-20-7]2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl)methyl]thiophene</strong> was sufficiently dissolved in 300 mL of tetrahydrofuran.At a temperature of -25 ° C to -20 ° C,100 g (0.245 mol) of sec-butylmagnesium chloride. Lithium chloride was added dropwise.After the addition was completed, the reaction was continued for 1 hour;Maintain temperature,Further, 171.6 g (0.368 mol) of 2,3,4,6-tetra-O-(trimethylsilyl)-D-gluconolactone was added dropwise.After the addition is completed,Continue to react for 2 hours;Wherein 2,3,4,6-tetra-O-(trimethylsilyl)-D-gluconolactone is previously dissolved in 200 mL of tetrahydrofuran;2) in the reaction liquid after the reaction in the step 1),51.8 g (0.539 mol) of methanesulfonic acid in methanol was added dropwise.Stir,After natural temperature reaction for 18 hours, at a temperature of -5 ° C to 5 ° C,The reaction was quenched with saturated aqueous sodium bicarbonate;3) adjusting the pH of the reaction solution after the reaction in step 2) with a saturated aqueous solution of sodium hydrogencarbonate to 7-8, and after removing the solvent under reduced pressure,Extracted with methyl n-butyl ether twice,Combine the organic phase,Dissolve the solvent under reduced pressure,Obtaining a yellow viscous solid crude;Add the crude product to 300 mL of methyl n-butyl ether.After fully dissolving, add 600 mL of n-heptane, stir, and precipitate a solid.The solvent was removed and dried under vacuum to obtain the intermediate of cagliflozin; 108.9 g of pale yellow solid was obtained, purity 87.9percent.The yield was 93.7percent.
(1) To a solution of <strong>[1030825-20-7]5-bromo-1-[5-(4-fluorophenyl)-2-thienylmethyl]-2-methylbenzene</strong> (1, 28.9 g) in tetrahydrofuran (480 ml) and toluene (480 ml) was added n-butyllithium (1.6M hexane solution, 50.0 ml) dropwise at -67 to -70 C. under argon atmosphere, and the mixture was stirred for 20 minutes at the same temperature. Thereto was added a solution of 2 (34.0 g) in toluene (240 ml) dropwise at the same temperature, and the mixture was further stirred for 1 hour at the same temperature. Subsequently, thereto was added a solution of methanesulfonic acid (21.0 g) in methanol (480 ml) dropwise, and the resulting mixture was allowed to warm to room temperature and stirred for 17 hours. The mixture was cooled under ice-water cooling, and thereto was added a saturated aqueous sodium hydrogen carbonate solution. The mixture was extracted with ethyl acetate, and the combined organic layer was washed with brine and dried over magnesium sulfate. The insoluble was filtered off and the solvent was evaporated under reduced pressure. The residue was triturated with toluene (100 ml)-hexane (400 ml) to give 1-(1-methoxyglucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]-benzene (3) (31.6 g). APCI-Mass m/Z 492 (M+NH4).
  • 2
  • [ 1030825-20-7 ]
  • 3,4,5-tris[(trimethylsilyl)oxy]-6-[(trimethylsilyl)oxy]methyl}-tetrahydro-2H-pyran-2-one [ No CAS ]
  • [ 1030825-21-8 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; methanesulfonic acid; sodium hydrogencarbonate; In methanol; hexane; dichloromethane; di-isopropyl ether; toluene; Example-1A Preparation of (3R,4S,5S,6R)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol (III) In 500 mL three necked round bottomed flask equipped with mechanical stirrer, thermometer and addition funnel were added 2-(5-bromo-2-methylbenzyl)-5-(4-fluorophenyl)thiophene (Va) (5 g) and 150 mL toluene at 25 C. 1.5 mL (1.6M) n-butyl lithium in hexane was added dropwise at room temperature and the solution was stirred for 30 minutes. This solution was cooled to -78 C. and added dropwise to a solution of 3,4,5-tris((trimethylsilyl)oxy)-6-(((trimethylsilyl)oxy)methyl)tetrahydro-2H-pyran-2-one (IV) (6.4 g) in 100 mL toluene and the mixture was stirred for 3 hours. The reaction mixture was treated with 2.5 g methanesulfonic acid in 100 mL methanol and stirred for 1 hour. The reaction mixture warmed to room temperature and stirred for 8 hours. Saturated sodium bicarbonate solution was added to the reaction mixture and the separated aqueous layer was extracted with toluene. The organic layer was distilled to remove toluene and the residue was dissolved in 50 mL methylene dichloride, washed with brine, dried over Na2SO4 and evaporated under reduced pressure to obtain residue. The residue was treated with 150 mL diisopropyl ether and stirred at 55 C. for 30 min, cooled, filtered and washed with diisopropyl ether to obtain compound of Formula (III).
With n-butyllithium; methanesulfonic acid; In methanol; hexane; toluene; Example-1 Preparation of (3R,4S,5S,6R)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol (III) In 500 mL three necked round bottomed flask equipped with mechanical stirrer, thermometer and addition funnel were added 2-(5-bromo-2-methylbenzyl)-5-(4-fluorophenyl)thiophene (Va) (5 g) and 150 mL toluene at 25 C. 1.5 mL (1.6M) n-butyl lithium in hexane was added dropwise at room temperature and the solution was stirred for 30 minutes. This solution was cooled to -78 C. and added dropwise to a solution of 3,4,5-tris((trimethylsilyl)oxy)-6-(((trimethylsilyl)oxy)methyl)tetrahydro-2H-pyran-2-one (IV) (6.4 g) in 100 mL toluene and the mixture was stirred for 3 hours. The reaction mixture was treated with 2.5 g methanesulfonic acid in 100 mL methanol and stirred for 1 hour. The reaction mass was warmed to 25 C. and then added to pre-cool saturated sodium bicarbonate solution and resulting mass was extracted with ethyl acetate. The extract was washed with brine, dried over Na2SO4 and evaporated under reduced pressure to obtain compound of Formula (III).
  • 3
  • [ 67-56-1 ]
  • [ 1030825-20-7 ]
  • [ 32469-28-6 ]
  • [ 1030825-21-8 ]
YieldReaction ConditionsOperation in experiment
92.1% Magnesium powder (12.0g, 500mmol), iodine (1.3g, 10.0mmol) was added to a dry reaction flask,The dried under nitrogen in tetrahydrofuran (50mL) was added to the reaction flask was cooled to 0 ,2 - [(5-bromo-2-methylphenyl) methyl] -5- (4-fluorophenyl) thiophene (II) (36.1g, 100mmol)In tetrahydrofuran (100mL) was slowly added dropwise to the reaction flask, plus complete warmed to 25 ,The reaction was stirred for 5 ~ 8h, cooled to 0 ,The above reaction solution at 0 ,Was added dropwise to 2,3,4,6-tetra (trimethylsilyl) -D- -O- gluconolactone (III) (55.9g,120mmol) in anhydrous tetrahydrofuran (100 mL) solution was added dropwise, and the reaction mixture was stirred for 2 ~ 3h,And under cooling with containing methanesulfonic acid (26.4g, 275mmol) in methanol (150 mL) was added dropwise to the reaction solution in the above,Bi dropwise slowly warmed to room temperature and stirred overnight.After completion of the reaction, the temperature dropped to 0 ,About 300mL saturated sodium bicarbonate solution was added to about pH 7, separated and the aqueous layer was extracted once with 200mL ethylThe combined organic layers with saturated brine (200 mL), washed once, dried over anhydrous magnesium sulfate, suction filtered,The filtrate was distilled under reduced pressure to give a paleYellow solid powder-methyl-1-C- (3 - ((5- (4- fluorophenyl) -2-thienyl) methyl) -4-methyl-phenyl) -D- glucopyranoside (I) 42.0g, yield 92.1percent, HPLC content of 95.9percent.
A solution of 2-(5-bromo-2-methylbenzyl)-5-(4-fluorophenyl)thiophene (100 g; Example 3) in tetrahydrofuran (200 mL) and toluene (300 mL) was added to a solution of -butyl lithium in hexane (3.2M; 76.8 g) and tetrahydrofuran (200 mL) at -75°C to -65°C under nitrogen atmosphere. The reaction mixture was stirred for 20 minutes to 40 minutes at the same temperature. A solution of 2,3,4,6-tetrakis-0-trimethylsilyl-D-glucono-l,5- lactone (194 g) in toluene (500 mL) was added to the reaction mixture at -70°C to -75°C, and then the mixture was stirred for 60 minutes to 90 minutes at the same temperature. A solution of methanesulphonic acid (66 g) in methanol (700 mL) was slowly added to the reaction mixture at -70°C to -75 °C. The reaction mixture was allowed to reach a temperature of 25°C to 30°C, and was then stirred at the same temperature for 12 hours. After completion of the reaction, the reaction mixture was washed with an aqueous solution of sodium bicarbonate (25 g of sodium bicarbonate in 500 mL of de-ionized water) at 25°C to 30°C. Ethyl acetate (500 mL) was added to the organic layer, and then the mixture was stirred for 10 minutes to 15 minutes. The reaction mixture was allowed to settle for 15 minutes, and then the layers were separated. The aqueous layer was washed twice with ethyl acetate (500 mL) and the layers were separated. The organic layers were combined, and then washed with an aqueous solution of sodium chloride (10 g of sodium chloride in 200 mL of de-ionized water). The organic layer was concentrated under reduced pressure at 45°C to obtain an oily residue. The oily residue was dissolved in toluene (300 mL) at 40°C to 45°C to obtain a solution. Hexane (1000 mL) was slowly added to the solution at 25 °C to 30°C under a nitrogen atmosphere. The mixture was stirred at the same temperature for 15 minutes to 20 minutes to obtain a solid. The solid was filtered under reduced pressure under nitrogen atmosphere, and then dried for 20 minutes to 30 minutes under nitrogen atmosphere to obtain l-(l-methoxyglucopyranosyl)- 4-methyl-3-[5-(4-flourophenyl)-2-thienylmethyl]benzene.
  • 4
  • [ 1030825-20-7 ]
  • [ 1030825-21-8 ]
  • 5
  • [ 75-75-2 ]
  • [ 1030825-20-7 ]
  • [ 32469-28-6 ]
  • [ 1030825-21-8 ]
YieldReaction ConditionsOperation in experiment
(1) replacing the reaction flask three times under inert gas N2,Add 300g of toluene, cool down to -70 ° C,97 g of n-butyllithium n-hexane solution (1.6 M, 1.08 eq) was added dropwise over 1 hour;Continue to add 2-(2-methyl-5-bromobenzyl)-5-(4-fluorophenyl)thiophene (68g) in a mixture of tetrahydrofuran (137g) and toluene (137g) within 1 hour The addition is completed;After reacting for 30 minutes, a mixed solution of 2,3,4,6-tetra-O-(trimethylsilyl)-D-glucono-delta-lactone (98 g) and toluene (279 g) was added dropwise.The addition was completed within 2 hours, and the reaction was kept for 3 hours after the completion of the dropwise addition;A mixed solution of methanesulfonic acid (48 g) and methanol (280 g) was added dropwise.After the completion of the dropwise addition, the temperature was raised to 10 ° C and the reaction was completed for 5 hours;Add saturated sodium bicarbonate solution to adjust pH 7-8, and separate the water layer.Extracting twice with ethyl acetate, washing with saturated brine and organic phase;The organic oil is removed by distillation under reduced pressure to a yellow oil, ie, an intermediate of formula I:
 

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