4-Bromophenol → 1-Bromo-4-{difluoro[4-(4,4,4-trifluorobutoxy)phenyl]methoxy}-benzene

HRID 511701Notes

Reaction equation

HRID 511701 reaction equation
FC(F)(F)S([O-])(=O)=O.[F:9][C:10]([F:28])([F:27])[CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2SCCC[S+]=2)=[CH:17][CH:16]=1.[Br:29][C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=1.C(N(CC)CC)C.[FH:44].[FH:45].F.C(N(CC)CC)C.BrBr>ClCCl>[Br:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][C:21]([F:45])([F:44])[C:18]2[CH:17]=[CH:16][C:15]([O:14][CH2:13][CH2:12][CH2:11][C:10]([F:9])([F:27])[F:28])=[CH:20][CH:19]=2)=[CH:32][CH:31]=1

Participants

7

Reactant 5

HCID 78084-BromophenolHCID 8471TriethylamineHCID 24408BromineHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 866765372-[4-(4,4,4-trifluorobutoxy)phenyl]-5,6-dihydro-4H-1,3-dithiin-1-ium trifluoromethanesulfonate

Product 1

HCID 866765401-Bromo-4-{difluoro[4-(4,4,4-trifluorobutoxy)phenyl]methoxy}-benzeneYield 67.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-55 °C

Procedure

77.0 g (164 mmol) of 2-[4-(4,4,4-trifluorobutoxy)phenyl]-5,6-dihydro-4H-1,3-dithiin-1-ium trifluoromethanesulfonate, are solubilised in 750 mL of dichloromethane. The solution is cooled down to −55° C. 42.5 g (245 mmol) of 4-bromophenol and 36.5 ml (262 mmol) of triethylamine dissolved in 300 ml of dichloromethane is added to the previous solution. The solution is cooled down to −70° C. and stirred for 45 minutes. 120 ml (736 mmol) of triethylamine trihydrofluoride are added to the mixture. A solution of 8.43 ml (164 mmol) of bromine in 60 ml of dichloromethane is added at this temperature. The reaction is stirred for one hour. The reaction is quenched by addition of NaHCO3. The organic phase is washed repeatedly with water, dried over sodium sulfate, filtrated and concentrated under reduced pressure. Chromatography of the residue on 400 g silica gel using toluene: ethyl acetate 95:5 as eluent yielded 47 g of 1-bromo-4-{difluoro[4-(4,4,4-trifluorobutoxy)phenyl]methoxy}-benzene.

Workup

  1. additionis added to the previous solution
  2. temperatureThe solution is cooled down to −70° C.
  3. stirringThe reaction is stirred for one hour
  4. customThe reaction is quenched by addition of NaHCO3
  5. washThe organic phase is washed repeatedly with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6cde6748121643adac7a39f569c5dcc6
Source dataset
uspto-grants-2015_08
Patent number
US09097938B2

Reaction notes

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