Sodium Thiosulfate → 2-(4-(2,2-Dimethyl-1,3-dioxan-5-yl)methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl-1H-benzimidazole

HRID 31713Notes

Reaction equation

HRID 31713 reaction equation
[CH3:1][C:2]1([CH3:29])[O:7][CH2:6][CH:5]([CH2:8][O:9][C:10]2[C:15]([CH3:16])=[CH:14][N:13]=[C:12]([CH2:17][S:18][C:19]3[NH:23][C:22]4[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=4[N:20]=3)[C:11]=2[CH3:28])[CH2:4][O:3]1.C(N(CC)C(C)C)(C)C.[O-]O.C1(C(C)C)C=CC=CC=1.C(=O)([O-])[OH:51].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C1(C)C=CC=CC=1.[O-]CCCC.[O-]CCCC.[O-]CCCC.[O-]CCCC.[Hf+4]>[CH3:1][C:2]1([CH3:29])[O:3][CH2:4][CH:5]([CH2:8][O:9][C:10]2[C:15]([CH3:16])=[CH:14][N:13]=[C:12]([CH2:17][S:18]([C:19]3[NH:20][C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[N:23]=3)=[O:51])[C:11]=2[CH3:28])[CH2:6][O:7]1

Participants

8

Reactant 5

HCID 24477Sodium ThiosulfateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 248807801H-Benzimidazole, 2-[[[4-[(2,2-dimethyl-1,3-dioxan-5-yl)methoxy]-3,5-dimethyl-2-pyridinyl]methyl]thio]-HCID 53627471Cumen hydroperoxide

Product 1

HCID 120032122-(4-(2,2-Dimethyl-1,3-dioxan-5-yl)methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl-1H-benzimidazoleYield 40%

Reagents, catalysts & solvents 2

HCID 10140113Hafnium(IV) n-butoxideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 2-(((4-((2,2-dimethyl-1,3-dioxan-5-yl)methoxy)-3,5-dimethylpyridin-2-yl)methyl)thio)-1H-benzimidazole (500 mg, 1.21 mmol) and N,N,N′,N′-(−)-tetramethyl-(D)-tartaramide (396 mg, 1.94 mmol) in toluene (4 ml) was dissolved by heating at 40° C. for 10 minutes in a nitrogen atmosphere. Hafnium tetrabutoxide (315 μL, 0.78 mmol) was added to the mixture and further stirred at the same temperature for one hour. After the reaction mixture was cooled to room temperature, N,N-diisopropylethylamine (90 μl, 0.52 mmol) was added and subsequently, cumene hydroperoxide (267 μl, 1.46 mmol as the content was regarded as 80%) was added dropwise to the mixture and then the mixture was stirred at room temperature for 22 hours. After a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium thiosulfate solution were added, the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtrated, and concentrated. The residue was purified by silica gel column chromatography (NH silica gel: 30 g, elution solvent: ethyl acetate, ethyl acetate/methanol 7:3, 1;1 gradient). The fractions containing the title compound were collected with ethyl acetate and concentrated to obtain the title compound (206 mg, yield: 40%) as a colorless foam.

Workup

  1. dissolutionwas dissolved
  2. temperatureAfter the reaction mixture was cooled to room temperature
  3. additionwas added dropwise to the mixture
  4. stirringthe mixture was stirred at room temperature for 22 hours
  5. extractionthe mixture was extracted with ethyl acetate
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography (NH silica gel: 30 g, elution solvent: ethyl acetate, ethyl acetate/methanol 7:3, 1;1 gradient)
  10. additionThe fractions containing the title compound
  11. customwere collected with ethyl acetate
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-0df9f35851a24d2cb8344f0a6a7219cf
Source dataset
uspto-grants-2008_09
Patent number
US07425634B2

Reaction notes

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