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Chemical Structure| 117976-47-3 Chemical Structure| 117976-47-3
Chemical Structure| 117976-47-3

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Product Details of Rabeprazole sulfone

CAS No. :117976-47-3
Formula : C18H21N3O4S
M.W : 375.44
SMILES Code : O=S(C1=NC2=CC=CC=C2N1)(CC3=NC=CC(OCCCOC)=C3C)=O
MDL No. :MFCD08063743

Safety of Rabeprazole sulfone

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P264-P270-P301+P312-P330-P501

Application In Synthesis of Rabeprazole sulfone

* 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 [ 117976-47-3 ]

[ 117976-47-3 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 117977-21-6 ]
  • 2-[(4-(3-methoxypropoxy)-3-methyl-pyridin-2-yl-1-oxide)methylsulfonyl]-1H-benzoimidazole [ No CAS ]
  • [ 117976-47-3 ]
  • 2
  • [ 117977-21-6 ]
  • [ 117976-89-3 ]
  • [ 117976-47-3 ]
YieldReaction ConditionsOperation in experiment
75 - 79%; 0.1 - 0.2% With sodium hydroxide; N-chloro-succinimide; water; In acetonitrile; at 0 - 5℃; for 2h;Product distribution / selectivity; Rabeprazole sulphide is added to aqueous sodium hydroxide solution at room temperature. Acetonitrile is added, stirred to obtain a solution. Cooled the solution to 0 to 50C and N-chlorosuccinimide is added slowly over a period of around 2 hr maintaining the temperature between 0 to 50C. After completion of the reaction, aqueous sodiumthiosulphate is added, adjusted the pH to 12.50 to 13.50 with sodium hydroxide, if needed. Added charcoal, stirred and filtered. Filtrate is extracted with dichloromethane to separate organic and aqueous layers. Aqueous layer is adjusted to pH 9.0 with ammonium acetate and extracted with dichloromethane. Combined dichloromethane layer is washed with 10% aqueous brine. Washed dichloromethane layer is treated with triethylamine and n-hexane. Mixture stirred at 20 to 250C. Solid obtained filtered, washed with a mixture of dichloromethane-n-hexane, dried to obtain sulphoxide compound Rabeprazole. Yield: 75-79% Purity: 99.64% Over oxidation Impurity: 0.1 to 0.2%
57%; 0.5 - 0.8% With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 20℃; for 1h;Product distribution / selectivity; To a solution of rabeprazole sulphide in dichloromethane is added a solution of m-chloroperbenzoic acid in dichloromethane maintaining the temperature at about - 2O0C and stirred for an hour. Water is added and pH adjusted to around 10.4 with 10% aqueous sodium hydroxide aqueous and organic layers are separated. Add water again, to organic layer, adjust the pH to 13.0 with aqueous 10% sodium hydroxide. Separate organic layer. Adjust the ph of aqueous layer to 9.5-10 with ammonium acetate solution and extract with dichloromethane. Distilling the organic layer under vacuum to obtain a residue, this is crystallized with acetone/ethyl acetate to get Rabeprazole. Yield: 57% Purity: 98.5 to 99% Over oxidation impurity: 0.5 to 0.8%
52 - 57%; 0.5 - 0.8% With sodium hypochlorite; water; In dichloromethane; at 0 - 5℃; for 3 - 6h;Product distribution / selectivity; Dichloromethane solvent is cooled to 0 to 50C and add rabeprazole sulphide and stirred to dissolve completely. Sodium hypochlorite solution (5% w/w) is added over a period of 1-2 h. The reaction mixture is further stirred between 0 to 50C for 2 to 4 h. Slowly the mixture is brought to room temperature. Adjusted the pH to 10.0 to 10.5 with ammonium sulphate. Separated the dichloromethane layer and extracted with 2.5% aqueous sodium hydroxide. Separated the aqueous layer and adjusted the pH to 8.7 to 9.2 with ammonium acetate solution. Extracted the pH adjusted aqueous layer with dichloromethane. Evaporated dichloromethane layer under vacuum at 20- 250C to obtain a residue. Dissolved the residue in ethyl-acetate and cooled to obtain sulphoxide compound (Rabeprazole). Yield: 52-57%; Purity: 98.5 to 99%; Over oxidation Impurity: 0.5 to 0.8%
  • 3
  • [ 117976-89-3 ]
  • [ 117976-47-3 ]
  • rabeprazol sulphone sodium salt [ No CAS ]
  • [ 117976-90-6 ]
YieldReaction ConditionsOperation in experiment
0.2%; 95% With sodium hydroxide; In methanol; at 0 - 50℃; for 4 - 5h;Product distribution / selectivity; Dissolve sodium hydroxide in methanol, stir to celerity. Add rabeprazole obtained in example 3 to it and stir at 45 - 5O0C for 4 to 5 h. Cool the reaction mixture to ca 250C, charge activated charcoal, stir and filter through celite bed. Collect the filtrate, distill under vacuum to remove methanol to obtain residue containing traces of methanol. Dissolve the residue in dichloromethane, add the solution with stirring to an alkane or ether solvent in an inert atmosphere to obtain amorphous powder of rabeproazole sodium which is dried under vacuum between 40-45C Yield: 95% Purity: 99.5% Sulphone impurity: 0.2% (highest single impurity) Example 5: Sodium hydroxide is dissolved in methanol at 250C to 350C for an hour. To this solution, rabeprazole obtained in example 3 is added at a temperature between 0 to 50C and stirred for 3 to 4 hours to dissolve it completely. Then activated charcoal is added, stirred and filtered through c elite b ed. The filtrate thus obtained is distilled under vacuum at 40-45C to remove methanol to obtain a thick residue. To this residue, alkane or ether solvent is added with stirring to obtain amorphous powder of rabeprazole sodium, which is dried under vacuum between 40 to 450C. Yield: 95% Purity: 99.5% Sulphone impurity: 0.2% (highest single impurity) Main advantages of the invention: 1) Provides process for obtaining rabeprazole in good yield and purity. 2) Provides process for preparing rabeprazole sodium exclusively in non-aqueous medium. 3) Provides simple and economical process for preparing rabeprazole sodium.
  • 4
  • [ 117977-21-6 ]
  • [ 117976-47-3 ]
  • 5
  • [ 117977-21-6 ]
  • S-(-)-Rabeprazole [ No CAS ]
  • [ 117976-47-3 ]
YieldReaction ConditionsOperation in experiment
0.73 g; 18%Chromat. With lithium 4-dimethylaminobenzoate; iron(III)-acetylacetonate; 2,4-dichloro-6-[(E)-[[(1S)-1-(hydroxymethyl)-2,2-dimethylpropyl]imino]methyl]phenol; dihydrogen peroxide; In water; ethyl acetate; at -5℃; for 21.5h; Example 18 Production of S-Rabeprazole 253 mg (874 mumol) of S-dichloro chiral ligand, 103 mg (291 mumol) of iron(III) acetylacetonate and 25.2 mg (147 mumol) of lithium 4-dimethylaminobenzoate were suspended in 5 mL ethyl acetate at 25 C., and stirred for more than 30 min. To the mixture were added 1.00 g (2.91 mmol) of the sulfide of rabeprazole and 5 mL ethyl acetate. After the mixture was cooled to -5 C. at a rate of 1 C. per min, 595 muL (5.82 mmol) of 30% aqueous hydrogen peroxide solution was added dropwise for more than 2 min. After 21.5 hours, the reaction mixture was analyzed under HPLC analysis condition 2 and HPLC analysis condition 3. <Content> sulfoxide 82%; sulfone 17%; sulfide 1% <Enantiomer excess of sulfoxide> 97% ee To the mixed solution was added 5 mL of the mixed solvent of a saturated aqueous sodium thiosulfate solution and a saturated aqueous sodium hydrogen carbonate. The mixture was heated to 5 C. and stirred. After removing the aqueous layer, the organic layer was concentrated under a reduced pressure. <Content> sulfoxide 82%; sulfone 18%; sulfide 0% <Enantiomer excess of sulfoxide> 97% ee After treatment by silica gel column chromatography (eluent: mixed solvent of ethyl acetate and methanol) was conducted to give 0.73 g of the title compound (purity 97%; 96% ee). 1H-NMR (400 MHz, DMSO): delta 13.5 (1H, s), 8.21 (1H, d), 7.65 (1H, br s), 7.31 (2H, m), 6.96 (1H, d), 4.75 (2H, q, -SOCH2-), 4.10 (2H, d), 3.48 (2H, t), 3.25 (3H, s), 2.14 (3H, s), 1.99 (2H, m) LRMS: [M+Na]+ Calcd. 382.12.
 

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