Water → HCID 21468979, compound

HRID 866247Notes

Reaction equation

HRID 866247 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:18]=[CH:17][C:12]2[N:13]=[C:14]([CH3:16])[NH:15][C:11]=2[CH:10]=1)#[N:2].[H-].[Na+].Br[CH:22]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[C:23]([O:25][CH2:26][CH3:27])=[O:24].O>CN(C=O)C.C(OCC)(=O)C>[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:18]=[CH:17][C:12]2[N:13]([CH:22]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:14]([CH3:16])=[N:15][C:11]=2[CH:10]=1)#[N:2]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 95580Ethyl 2-bromooctanoateHCID 21468895HCID 21468895, compound

Product 1

HCID 21468979HCID 21468979, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-(2-Cyanophenyl)-2-methylbenzimidazole (3.43 mmoles, 0.8 g) was dissolved in DMF. Sodium hydride (3.75 mmoles, 0.15 g.) was added. The solution was stirred for 30 minutes. Ethyl 2-bromooctanoate was added. The solution was stirred for 1 hour. Water and ethyl acetate were added; and the layers separated. The organic phase was washed with brine, dried over sodium sulfate and concentrated. The intermediate was chromatographed on silica gel eluted with 50% ethyl acetate in hexane to yield 1.0 g of ethyl 2-[5-[2-cyanophenyl]-2-methyl-1H-benzimidazol-1-yl]octanoate. The nitrile was dissolved in 10 ml of tributyltinazide and heated at 70° C. for 3 days. The solution was stirred in a mixture of acetonitrile, water, and acetic acid (100 ml of 8:1:1) for 3 hours, washed with hexane (4×250 ml), and concentrated. The residue was dissolved in ethyl acetate, washed with water, dried over sodium sulfate and concentrated in vacuo. The intermediate was triturated with hexane, filtered and chromatographed over silica gel eluted with 10% ethanol in ethyl acetate with 1% acetic acid. The isomers were separated by reverse phase HPLC eluted with a gradient of 30-50% acetonitrile in water with 1% ammonium acetate. The intermediate was dissolved in ethanol (20 ml) and 5N NaOH (5 ml) and heated on a steam bath for 1 hour. The solution was concentrated to 75 ml. The pH was adjusted to 3.0 using 5N HCl. The precipitate was collected and dried. The reaction yielded 110 mg of 2-[5-[2-(2H-tetrazol-5-yl)phenyl]-2-methyl-1H-benzimidazol-1-yl]octanoic acid. (MS)

Workup

  1. stirringThe solution was stirred for 1 hour
  2. customand the layers separated
  3. washThe organic phase was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe intermediate was chromatographed on silica gel
  7. washeluted with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-eede264c4cd44571942a5b126029b42c
Source dataset
uspto-grants-1996_10
Patent number
US05569768

Reaction notes

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