Water → N-(4-Benzyloxy-2-fluorophenyl)-N'-(4-fluorophenyl)-N-methylurea

HRID 388023

Reaction equation

HRID 388023 reaction equation
[CH3:1][NH:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:5][C:4]=1[F:17].[H-].[Na+].[F:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]=[C:28]=[O:29])=[CH:23][CH:22]=1.O>CN(C)C=O.C(OCC)(=O)C>[CH2:10]([O:9][C:6]1[CH:7]=[CH:8][C:3]([N:2]([CH3:1])[C:28]([NH:27][C:24]2[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=2)=[O:29])=[C:4]([F:17])[CH:5]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 709554-Fluorophenyl isocyanate2×HCID 22936658N-Methyl-4-benzyloxy-2-fluoroaniline

Product 1

HCID 22936494N-(4-Benzyloxy-2-fluorophenyl)-N'-(4-fluorophenyl)-N-methylureaYield 26.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

N-Methyl-4-benzyloxy-2-fluoroaniline (250 mg, 1.0805 mmol) was dissolved in N,N-dimethylformamide (5.0 ml), and then sodium hydride (65 mg, 1.6207 mmol, 60% in oil) was added and the mixture was stirred at 95° C. for 45 minutes under a nitrogen atmosphere. After adding 4-fluorophenyl isocyanate (0.14 ml, 1.1836 mmol), the mixture was stirred at 85° C. for 45 minutes under a nitrogen atmosphere. There was further added 4-fluorophenyl isocyanate (0.14 ml, 0.5094 mmol), and the mixture was stirred at 85° C. for 30 minutes under a nitrogen atmosphere. After cooling to room temperature, water was added to the reaction solution, extraction was performed with ethyl acetate, the extract was washed with saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was adsorbed onto NH silica gel and purified by NH silica gel column chromatography (hexane-ethyl acetate system) to obtain the title compound (0.105 g, 0.2881 mmol, 21.67%) as a light yellow oil.

Workup

  1. stirringthe mixture was stirred at 85° C. for 45 minutes under a nitrogen atmosphere
  2. stirringthe mixture was stirred at 85° C. for 30 minutes under a nitrogen atmosphere
  3. temperatureAfter cooling to room temperature
  4. washthe extract was washed with saturated saline
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. custompurified by NH silica gel column chromatography (hexane-ethyl acetate system)

Sources & evidence

ORD record
ord-23cec06d6e4548f289965501a4c4ca28
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Linked notes

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