Lithium Hydroxide → (Z)-2-[8-(2-ethyl-4,6-dimethylbenzimidazol-1-yl)methyl-6,11-dihydrodibenzo[b,e]oxepin-11-ylidene]propiononitrile

HRID 885445Notes

Reaction equation

HRID 885445 reaction equation
O[CH2:2][C:3]1[CH:21]=[CH:20][C:6]2/[C:7](=[C:16](\[CH3:19])/[C:17]#[N:18])/[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[O:10][CH2:11][C:5]=2[CH:4]=1.N1C(C)=CC=CC=1C.[Br-].[Li+].CS(OS(C)(=O)=O)(=O)=O.[CH2:41]([C:43]1[NH:44][C:45]2[C:51]([CH3:52])=[CH:50][C:49]([CH3:53])=[CH:48][C:46]=2[N:47]=1)[CH3:42].[OH-].[Li+]>C1COCC1.CN(C=O)C.C(OCC)(=O)C>[CH2:41]([C:43]1[N:47]([CH2:2][C:3]2[CH:21]=[CH:20][C:6]3/[C:7](=[C:16](\[CH3:19])/[C:17]#[N:18])/[C:8]4[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=4[O:10][CH2:11][C:5]=3[CH:4]=2)[C:46]2[CH:48]=[C:49]([CH3:53])[CH:50]=[C:51]([CH3:52])[C:45]=2[N:44]=1)[CH3:42]

Participants

10

Reactant 6

HCID 3939Lithium HydroxideHCID 79372,6-LutidineHCID 81560Methanesulfonic anhydrideHCID 82050Lithium BromideHCID 67211541(Z)-2-(8-hydroxymethyl-6,11-dihydrodibenzo[b,e]oxepin-11-ylidene)propiononitrileHCID 178437417HCID 178437417, compound

Product 1

HCID 69016149(Z)-2-[8-(2-ethyl-4,6-dimethylbenzimidazol-1-yl)methyl-6,11-dihydrodibenzo[b,e]oxepin-11-ylidene]propiononitrileYield 93.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

[step 1] (Z)-2-(8-Hydroxymethyl-6,11-dihydrodibenzo[b,e]oxepin-11-ylidene)propiononitrile (150 mg, 0.54 mmol) was dissolved in THF (5.5 mL), and the solution was added with 2,6-lutidine (0.378 mL, 3.25 mmol), lithium bromide (282 mg, 3.25 mmol) and methanesulfonic anhydride (236 mg, 1.35 mmol), followed by stirring at room temperature for 16 hr. Ethyl acetate was added to the mixture, and the organic layer was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a residue. The obtained residue and 2-ethyl-4,6-dimethylbenzimidazole (123 mg, 0.71 mmol) were dissolved in DMF (3.0 mL) and the solution was added with lithium hydroxide (24 mg, 0.98 mmol) at 0° C., followed by stirring at room temperature for 2 hr. Ethyl acetate was added to the mixture, and the organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=7/3-6/4) to give (Z)-2-[8-(2-ethyl-4,6-dimethylbenzimidazol-1-yl)methyl-6,11-dihydrodibenzo[b,e]oxepin-11-ylidene]propiononitrile (219 mg, 93%).

Workup

  1. washthe organic layer was washed with brine
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto give a residue
  5. stirringby stirring at room temperature for 2 hr
  6. washthe organic layer was washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=7/3-6/4)

Sources & evidence

ORD record
ord-a60df5103ded442c979568cf1141e84a
Source dataset
uspto-grants-2012_08
Patent number
US08242151B2

Reaction notes

Loading…