Water → 2-(((3-methyl-4-(1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole

HRID 1645566Notes

Reaction equation

HRID 1645566 reaction equation
O.[CH3:2][C:3]1[C:4]([CH2:22][S:23][C:24]2[NH:28][C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[N:25]=2)=[N:5][CH:6]=[CH:7][C:8]=1[O:9][CH2:10][CH:11]1[CH2:16][O:15][C:14]2([CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[O:13][CH2:12]1.C(N(CC)C(C)C)(C)C.[O-]O.C1(C(C)C)C=CC=CC=1.C(=O)([O-])[OH:54].[Na+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C1(C)C=CC=CC=1>[CH3:2][C:3]1[C:4]([CH2:22][S:23]([C:24]2[NH:25][C:26]3[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=3[N:28]=2)=[O:54])=[N:5][CH:6]=[CH:7][C:8]=1[O:9][CH2:10][CH:11]1[CH2:16][O:15][C:14]2([CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)[O:13][CH2:12]1

Participants

8

Reactant 5

HCID 962WaterHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 53627471Cumen hydroperoxideHCID 597925582-(((3-methyl-4-(1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy)pyridin-2-yl)methyl)thio)-1H-benzimidazole2×

Product 1

HCID 120032132-(((3-methyl-4-(1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzimidazoleYield 82.4%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

To a toluene (dehydrated) (1.5 ml)-water (1.47 μl, 81.5 μmol) solution of the 2-(((3-methyl-4-(1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy)pyridin-2-yl)methyl)thio)-1H-benzimidazole (300 mg, 679 μmol) separately obtained in the same manner as described in the steps (10a) to (10d) of Example 10, L-(+)-diethyl tartrate (51.2 μl, 299 μmol) was added and the mixture was stirred at 50° C. for 5 minutes in a nitrogen atmosphere. Titanium (IV) isopropoxide (40.1 μl, 136 μmol) was added and the resultant mixture was stirred for further one hour. After cooled on ice and N,N-diisopropylethylamine (37.8 μl, 217 μmol) was added, and cumene hydroperoxide (376 μl, 2.04 mmol as the content was regarded as 80%) was added dropwise in a nitrogen atmosphere, the mixture was stirred at 0° C. to room temperature for 5.5 hours. After a saturated aqueous solution of sodium hydrogen carbonate was added, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/methanol) to obtain the title compound (256 mg, yield: 82.4%) as a light yellow foam.

Workup

  1. additionwas added
  2. additionwas added
  3. additionwas added dropwise in a nitrogen atmosphere
  4. stirringthe mixture was stirred at 0° C. to room temperature for 5.5 hours
  5. extractionthe reaction mixture was extracted with ethyl acetate
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/methanol)

Sources & evidence

ORD record
ord-6f9e440d84d7468c8d020647f05a0988
Source dataset
uspto-grants-2012_02
Patent number
US08124780B2

Reaction notes

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