(3-Bromo-4-fluorophenyl)(4-fluoro-2-(1,1,2,2-tetrafluoroethoxy)phenyl)methanol → (3-Bromo-4-fluorophenyl)(4-fluoro-2-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

HRID 238776Notes

Reaction equation

HRID 238776 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[O:18][C:19]([F:24])([F:23])[CH:20]([F:22])[F:21])[OH:10])[CH:5]=[CH:6][C:7]=1[F:8]>ClCCl.O=[Mn]=O>[Br:1][C:2]1[CH:3]=[C:4]([C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[O:18][C:19]([F:23])([F:24])[CH:20]([F:21])[F:22])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 1

HCID 86613050(3-Bromo-4-fluorophenyl)(4-fluoro-2-(1,1,2,2-tetrafluoroethoxy)phenyl)methanol

Product 1

HCID 86613051(3-Bromo-4-fluorophenyl)(4-fluoro-2-(1,1,2,2-tetrafluoroethoxy)phenyl)methanoneYield 60%

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalyst3×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (5.0 g, 17 mmol) in ether (40 mL) at −78° C. was added a solution of n-butyllithium (6.9 mL, 2.5 M, 17 mmol). The reaction mixture was stirred for 15 minutes and was added a solution of 3-bromo-4-fluorobenzaldehyde (3.5 g, 17 mmol) in ether (10 mL). The reaction was stirred at −78° C. for 2 h, then quenched with sat. NH4Cl and warmed to room temperature. The ether layer was separated and dried over magnesium sulfate, filtered and concentrated to yield (3-bromo-4-fluorophenyl)(4-fluoro-2-(1,1,2,2-tetrafluoroethoxy)phenyl)methanol as an amber oil (6.5 g, 92% yield). The product was used in the next step without further purification. To a solution of (3-bromo-4-fluorophenyl)(4-fluoro-2-(1,1,2,2-tetrafluoroethoxy)phenyl)methanol (29.5 g, 71.3 mmol) in dichloromethane (600 mL) was added MnO2 (30 g, 345 mmol). The reaction mixture was stirred for 6 h, then another 30 g of MnO2 was added and the reaction continued to stir overnight. The MnO2 addition was repeated twice and the reaction was stirred for a total of 48 h when the reaction was complete. The suspension was filtered through a pad of celite, the filtrate vas concentrated and the residue was purified by ISCO flash chromatography to yield (3-bromo-4-fluorophenyl)(4-fluoro-2-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone as a yellow oil (60% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.06 (1H, d, J=6.59 Hz), 7.76 (1H, ddd, J=6.48, 4.50, 2.20 Hz), 7.38-7.44 (2H, m), 7.21-7.29 (2H, m), 6.09-5.83 (1H, t).

Workup

  1. customThe product was used in the next step without further purification
  2. stirringto stir overnight
  3. stirringthe reaction was stirred for a total of 48 h when the reaction
  4. filtrationThe suspension was filtered through a pad of celite
  5. concentrationthe filtrate vas concentrated
  6. customthe residue was purified by ISCO flash chromatography

Sources & evidence

ORD record
ord-04b24305875d40ea926a061f3c0c6c99
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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