Methyl iodide → (2-Bromo-5-fluoro-phenyl)-methyl-carbamic acid tert-butyl ester

HRID 1513982Notes

Reaction equation

HRID 1513982 reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[Br:15])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:20]>CN(C)C=O>[C:1]([O:5][C:6](=[O:16])[N:7]([C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[Br:15])[CH3:20])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57552565HCID 57552565, compound

Product 1

HCID 57552511(2-Bromo-5-fluoro-phenyl)-methyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Place (2-bromo-5-fluoro-phenyl)-carbamic acid tert-butyl ester (2.00 g, 6.90 mmol) and dimethylformamide (40 mL) in a round bottom flask. Cool the solution to 0° C., add sodium hydride (60% dispersion in mineral oil) (0.303 g, 7.59 mmol), remove the ice bath and stir this suspension for 25 minutes allowing it to warm slowly towards ambient temperature. Cool the resulting mixture to 0° C. once again, and add iodomethane (0.56 mL, 8.96 mmol). Stir the resulting mixture overnight, allowing it to warm to ambient temperature. Quench the reaction with brine and extract the resulting mixture into ethyl acetate. Combine the extracts and wash with brine; then dry (sodium sulfate) and concentrate in vacuo. Purify the resulting material by flash chromatography (silica gel; 35%-50% dichloromethane gradient in hexanes) to provide the desired product.

Workup

  1. customremove the ice bath
  2. temperatureto warm slowly towards ambient temperature
  3. temperatureCool the resulting mixture to 0° C. once again
  4. stirringStir the resulting mixture overnight
  5. temperatureto warm to ambient temperature
  6. customQuench
  7. customthe reaction with brine
  8. extractionextract the resulting mixture into ethyl acetate
  9. washwash with brine
  10. dry with materialthen dry (sodium sulfate)
  11. concentrationconcentrate in vacuo
  12. customPurify the resulting material by flash chromatography (silica gel; 35%-50% dichloromethane gradient in hexanes)

Sources & evidence

ORD record
ord-b4c212642cf94c01a00b2bb951a576a7
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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