Hydrochloric Acid → 4-(p-Chlorophenyl)-2,3-difluoro-5-methyl-1-(m-phenoxyphenyl)-2-hexene

HRID 1977722Notes

Reaction equation

HRID 1977722 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:13]([CH3:15])[CH3:14])[C:9]([F:12])=[CH:10][F:11])=[CH:4][CH:3]=1.C([Li])CCC.[C:21]1([O:27][C:28]2[CH:29]=[C:30]([CH2:34]Br)[CH:31]=[CH:32][CH:33]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl>O1CCCC1.CCCCCC.O.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCCCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH:13]([CH3:15])[CH3:14])[C:9]([F:12])=[C:10]([F:11])[CH2:34][C:30]2[CH:31]=[CH:32][CH:33]=[C:28]([O:27][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:29]=2)=[CH:6][CH:7]=1

Participants

11

Reactant 4

HCID 313Hydrochloric AcidHCID 945441-(Bromomethyl)-3-phenoxybenzeneHCID 542868233-(p-Chlorophenyl)-1,2-difluoro-4-methyl-1-penteneHCID 178418339Butyllithium

Product 1

HCID 538935154-(p-Chlorophenyl)-2,3-difluoro-5-methyl-1-(m-phenoxyphenyl)-2-hexene

Reagents, catalysts & solvents 6

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolvent

Conditions

Temperature
-60 °C

Procedure

A solution of 3-(p-chlorophenyl)-1,2-difluoro-4-methyl-1-pentene (0.69 g, 0.003 mol) in tetrahydrofuran is cooled to −70° C., treated with a 2.5 M solution of n-butyllithium in hexane (1.2 mL), stirred at −60° C. for 1 hour, treated with a 0.5 M solution of zinc chloride in tetrahydrofuran (6 mL), stirred at −60° C. for 1 hour, treated sequentially with a solution of tetrakis(triphenylphosphine)palladium(0) (0.081 g) in tetrahydrofuran and a solution of α-bromo-m-tolyl phenyl ether (0.789 g, 0.003 mol) in tetrahydrofuran, stirred at room temperature overnight, diluted with water, acidified with 10% hydrochloric acid, and extracted with methylene chloride. The combined organic extracts are washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain an oil. Column chromatography of the oil using silica gel and pentane affords an oil which is purified by Kugelrohr distillation to give the title product as a pale, yellow oil (0.46 g) which is identified by NMR spectral analyses.

Workup

  1. stirringstirred at −60° C. for 1 hour
  2. extractionextracted with methylene chloride
  3. washThe combined organic extracts are washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto obtain an oil
  7. customaffords an oil which
  8. distillationis purified by Kugelrohr distillation

Sources & evidence

ORD record
ord-1a2e81f587314cd6b42128f116242eb1
Source dataset
uspto-grants-2001_05
Patent number
US06235754B1

Reaction notes

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