Dimethylformamide → 4-(4-Bromo-2-butyl-5-formyl-imidazol-1-ylmethyl)-2,3-difluorobenzoic acid methyl ester

HRID 919322Notes

Reaction equation

HRID 919322 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10]Br)=[C:6]([F:12])[C:5]=1[F:13].[Br:15][C:16]1[N:20]=[C:19]([CH2:21][CH2:22][CH2:23][CH3:24])[NH:18][C:17]=1[CH:25]=[O:26].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:18]2[C:17]([CH:25]=[O:26])=[C:16]([Br:15])[N:20]=[C:19]2[CH2:21][CH2:22][CH2:23][CH3:24])=[C:6]([F:12])[C:5]=1[F:13]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 57435562Methyl 4-(bromomethyl)-2,3-difluorobenzoateHCID 178441570HCID 178441570, compound

Product 1

HCID 866243614-(4-Bromo-2-butyl-5-formyl-imidazol-1-ylmethyl)-2,3-difluorobenzoic acid methyl esterYield 75.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

4-bromomethyl-2,3-difluorobenzoic acid methyl ester (3.5 g, 13.2 mmol), 5-bromo-2-butyl-3H-imidazole-4-carbaldehyde (3.1 g, 13.2 mmol) and potassium carbonate (1.8 g, 13.2 mmol) were combined and dissolved in DMF (20 mL, 300 mmol). The mixture was stirred at room temperature overnight. The mixture was then diluted with water and extracted with EtOAc. The organic layer was washed with saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated. The crude reaction was purified by silica gel chromatography (0-50% EtOAc:hexanes) to obtain 4.16 g of intermediate (8a) as a yellow solid. MS m/z: [M+H+] calcd for C17H17BrF2N2O3, 416.23. found 417.1. 1H-NMR (CDCl3): 9.68 (1H, s), 7.64 (1H, t), 6.55 (1H, t), 5.64 (2H, s), 3.95 (3H, s), 2.63 (2H, t), 1.69 (2H, m), 1.36 (2H, m) 0.90 (3H, t).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with saturated aqueous NaCl
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude reaction
  7. customwas purified by silica gel chromatography (0-50% EtOAc:hexanes)

Sources & evidence

ORD record
ord-c506cecde2f646e1a611aeb9f127de19
Source dataset
uspto-grants-2016_03
Patent number
US09273008B2

Reaction notes

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