1-Bromo-2-methylpropane → 7-iodo-3-isobutyl-3H-benzoimidazole-5-carboxylic acid methyl ester

HRID 59814Notes

Reaction equation

HRID 59814 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]([I:14])[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=[O:4].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:21](Br)[CH:22]([CH3:24])[CH3:23]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]([I:14])[C:8]2[N:9]=[CH:10][N:11]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:7]=2[CH:6]=1)=[O:4].[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]([I:14])[C:8]2[N:9]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH:10]=[N:11][C:7]=2[CH:6]=1)=[O:4]

Participants

6

Reactant 3

HCID 65551-Bromo-2-methylpropaneHCID 10796Cesium carbonateHCID 596277711H-Benzimidazole-5-carboxylic acid, 7-iodo-, methyl ester

Product 2

HCID 596277737-iodo-3-isobutyl-3H-benzoimidazole-5-carboxylic acid methyl esterYield 87%HCID 675166697-iodo-1-isobutyl-1H-benzoimidazole-5-carboxylic acid methyl esterYield 11%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 7-iodo-3H-benzoimidazole-5-carboxylic acid methyl ester (783 mg, 2.59 mmol) in DMF (50 mL) was added Cs2CO3 (1.69 g, 5.18 mmol), followed by isobutyl bromide ((0.338 mL, 3.11 mmol). The reaction mixture was stirred room temperature overnight, then partitioned between water and ethyl acetate. The organic layer was separated, dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue by column chromatography gave 805 mg (87%) of 7-iodo-3-isobutyl-3H-benzoimidazole-5-carboxylic acid methyl ester (the regioisomer 7-iodo-1-isobutyl-1H-benzoimidazole-5-carboxylic acid methyl ester (100 mg, 11%) was recovered as separate fraction).

Workup

  1. custompartitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue by column chromatography

Sources & evidence

ORD record
ord-f35964f64c2f431bab37e6cd83ff0cf5
Source dataset
uspto-grants-2016_09
Patent number
US09440956B2

Reaction notes

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