Water → 4-Benzyloxy-N-[3,5-bis(trifluoromethyl)phenyl]isophthalamic acid methyl ester

HRID 421074Notes

Reaction equation

HRID 421074 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:30])[C:6]1[CH:28]=[CH:27][C:26]([OH:29])=[C:8]([C:9]([NH:11][C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=2)=[O:10])[CH:7]=1.[CH2:31](Br)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.O>CCCCCC.CN(C)C=O>[CH3:3][O:4][C:5](=[O:30])[C:6]1[CH:28]=[CH:27][C:26]([O:29][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[C:8]([C:9]([NH:11][C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:19])[F:20])[CH:15]=[C:14]([C:22]([F:23])([F:24])[F:25])[CH:13]=2)=[O:10])[CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 11327249N-[3,5-Bis(trifluoromethyl)phenyl]-4-hydroxyisophthalamic acid methyl ester

Product 1

HCID 865955364-Benzyloxy-N-[3,5-bis(trifluoromethyl)phenyl]isophthalamic acid methyl esterYield 54.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8058HexaneSolvent

Procedure

Sodium hydride (60%; 1.04 g, 26 mmol) was washed with n-hexane, suspended in N,N-dimethylformamide (100 mL). A solution of N-[3,5-bis(trifluoromethyl)-phenyl]-4-hydroxyisophthalamic acid methyl ester (8.15 g, 20 mmol) in N,N-dimethylformamide (100 mL) was added dropwise under cooling with ice bath. After the addition was finished, the mixture was stirred at room temperature for 1 hour. A solution of benzyl bromide (4.45 g, 26 mmol) in N,N-dimethylformamide (10 mL) was added, and the mixture was stirred at 60° C. for 3 hours. After cooling, the reaction mixture was poured into ice and water, and extracted with ethyl acetate. After the organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, the residue obtained by evaporation under reduced pressure was recrystallized (ethyl acetate/n-hexane) to give the title compound (5.38 g, 54.1%) as a white solid.

Workup

  1. temperatureunder cooling with ice bath
  2. additionAfter the addition
  3. stirringthe mixture was stirred at 60° C. for 3 hours
  4. temperatureAfter cooling
  5. extractionextracted with ethyl acetate
  6. washAfter the organic layer was washed with water and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe residue obtained by evaporation under reduced pressure
  9. customwas recrystallized (ethyl acetate/n-hexane)

Sources & evidence

ORD record
ord-58e38933007f4ee2823e65b60b07049b
Source dataset
uspto-grants-2012_01
Patent number
US08097759B2

Reaction notes

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