Acetyl chloride → HCID 69719682, compound

HRID 896384Notes

Reaction equation

HRID 896384 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([CH2:14][O:15]C(=O)C)[NH:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:25](I)[CH2:26][CH:27]([CH3:29])[CH3:28].C(Cl)(=O)C>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([CH2:14][OH:15])[N:10]([CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28])[C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 10796Cesium carbonateHCID 109241-Iodo-3-methylbutaneHCID 20814102HCID 20814102, compound

Product 1

HCID 69719682HCID 69719682, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 2-acetoxymethyl-1H-benzoimidazole-4-carboxylic acid methyl ester (2.09 g, 8.42 mmol) and cesium carbonate (4.1 g, 12.6 mmol) in DMF (15 mL) at ambient temperature was added isoamyl iodide (1.34 mL, 10.1 mmol). The mixture was stirred overnight and DMF was removed in vacuo. The residue was suspended in water and extracted with ethyl acetate (twice), the combined organic phases were washed with brine, dried (MgSO4) and concentrated. The residue (2-acetoxymethyl-1-(3-methyl-butyl)-1H-benzoimidazole-4-carboxylic acid methyl ester) was dissolved in methanol (20 mL) and cooled to 0° C., followed by the addition of acetyl chloride (6.0 mL, 84 mmol) and slowly allowed to reach room temperature. After stirring for 3 hrs the volatiles were removed in vacuo and the residue triturated in ethyl acetate to afford 2-hydroxymethyl-1-(3-methyl-butyl)-1H-benzoimidazole-4-carboxylic acid methyl ester after filtration (1.98 g, 85% over 2 steps) as a white solid. 1H NMR Analysis of the crude acetate indicated that the desired N-1 regioisomer was contaminated with the N-3 isomer (ca. 15%), which was efficiently eliminated by the ethyl acetate wash (<2%). The 1H NMR spectral data of the regioisomeric impurity 2-acetoxymethyl-3-(3-methyl-butyl)-3H-benzoimidazole-4-carboxylic acid methyl ester matched those of an authentic sample prepared via an independent route.

Workup

  1. customDMF was removed in vacuo
  2. extractionextracted with ethyl acetate (twice), the combined organic phases
  3. washwere washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. dissolutionThe residue (2-acetoxymethyl-1-(3-methyl-butyl)-1H-benzoimidazole-4-carboxylic acid methyl ester) was dissolved in methanol (20 mL)
  7. customto reach room temperature
  8. stirringAfter stirring for 3 hrs the volatiles
  9. customwere removed in vacuo
  10. customthe residue triturated in ethyl acetate

Sources & evidence

ORD record
ord-55c17e0776b8456ca8f34b923935b0e3
Source dataset
uspto-grants-2005_07
Patent number
US06919331B2

Reaction notes

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