Methyl iodide → (4-Bromo-3,5-dimethyl-phenyl)-methyl-carbamic acid tert-butyl ester

HRID 1755016Notes

Reaction equation

HRID 1755016 reaction equation
IC.[C:3]([O:7][C:8](=[O:19])[NH:9][C:10]1[CH:15]=[C:14]([CH3:16])[C:13]([Br:17])=[C:12]([CH3:18])[CH:11]=1)([CH3:6])([CH3:5])[CH3:4].[C:20](=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[NH4+]>CN(C=O)C>[C:3]([O:7][C:8](=[O:19])[N:9]([C:10]1[CH:11]=[C:12]([CH3:18])[C:13]([Br:17])=[C:14]([CH3:16])[CH:15]=1)[CH3:20])([CH3:6])([CH3:5])[CH3:4]

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 10796Cesium carbonate2×HCID 25517Ammonium ChlorideHCID 22662122tert-Butyl (4-bromo-3,5-dimethylphenyl)carbamate

Product 1

HCID 66818385(4-Bromo-3,5-dimethyl-phenyl)-methyl-carbamic acid tert-butyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Iodomethane (20.5 ml, 329 mmol) was added to a solution of (4-bromo-3,5-dimethyl-phenyl)-carbamic acid tert-butyl ester (47.5 g, 158 mmol) and cesium carbonate (80.6 g, 247 mmol) in DMF (165 ml) at room temperature, and the mixture was stirred for 27 hours. Further, cesium carbonate (26.9 g, 82.6 mmol) and iodomethane (20.5 ml, 329 mmol) were added at room temperature, and the mixture was further stirred for three days. An aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was sequentially washed with water and saturated brine and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give (4-bromo-3,5-dimethyl-phenyl)-methyl-carbamic acid tert-butyl ester (9.34 g, 92%).

Workup

  1. stirringthe mixture was further stirred for three days
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was sequentially washed with water and saturated brine
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-14744e01deb84a1197688d478e106ac9
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

Loading…