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

HRID 1479783Notes

Reaction equation

HRID 1479783 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)benzamide2×

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 stifling 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. customwith stifling via a syringe 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-a61662bdbfd04e72ace05ece62c29591
Source dataset
uspto-grants-2016_08
Patent number
US09409856B2

Reaction notes

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