Water → 4-fluoro-N,N-bis(4-hydroxyphenyl)-2-(trifluoromethyl)benzamide

HRID 1037153Notes

Reaction equation

HRID 1037153 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][C:5]([C:6]([N:8]([C:17]2[CH:22]=[CH:21][C:20]([O:23]C)=[CH:19][CH:18]=2)[C:9]2[CH:14]=[CH:13][C:12]([O:15]C)=[CH:11][CH:10]=2)=[O:7])=[C:4]([C:27]([F:30])([F:29])[F:28])[CH:3]=1.B(Br)(Br)Br.O.CCOC(C)=O>C(Cl)Cl>[F:1][C:2]1[CH:26]=[CH:25][C:5]([C:6]([N:8]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[O:7])=[C:4]([C:27]([F:28])([F:29])[F:30])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 25134Boron tribromideHCID 668231144-fluoro-N,N-bis(4-methoxyphenyl)-2-(trifluoromethyl)benzamide

Product 1

HCID 573882934-fluoro-N,N-bis(4-hydroxyphenyl)-2-(trifluoromethyl)benzamideYield 92.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Compound 4-fluoro-N,N-bis(4-methoxyphenyl)-2-(trifluoromethyl)benzamide (2e) (1.00 g, 2.38 mmol) was dissolved in dry CH2Cl2 (30 mL) at room temperature. BBr3 (10 mL of 1.0 M CH2Cl2 solution, 10.0 mmol) was added dropwise with stirring via a syringe at room temperature. The reaction solution was allowed to stir overnight at room temperature. The mixture was cooled to 0° C. in an ice bath and hydrolyzed by adding water. EtOAc was added to partition the solution. The organic layer was separated; the aqueous layer was extracted with EtOAc twice. The organic layers were combined, washed with brine and dried over anhydrous MgSO4. The solvent was removed under vacuum. The residue was purified by flash column chromatography using silica-gel with CH3OH/CH2Cl2 (1/9 v/v) to afford the pure desired phenolic compound as a white solid, 0.86 g, 92.5% yield. 1H NMR (DMSO-d6, 300 MHz) δ 9.55 (s, 1H), 9.53 (s, 1H), 7.69-7.58 (m, 2H), 7.46-7.39 (m, 1H), 7.18 (d, 2H, J=8.7 Hz), 6.93 (d, 4H, J=8.7 Hz), 7.03 (d, 2H, J=8.4 Hz), 6.78 (d, 2H, J=8.7 Hz), 6.57 (d, 2H, J=8.7 Hz). MS m/z 392.1(M+H)+.

Workup

  1. stirringto stir overnight at room temperature
  2. temperatureThe mixture was cooled to 0° C. in an ice bath
  3. customto partition the solution
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc twice
  6. washwashed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. customThe solvent was removed under vacuum
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-58382b41a7a84556b55d644ed20cf310
Source dataset
uspto-grants-2013_10
Patent number
US08546451B2

Reaction notes

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