Potassium Phosphate, Tribasic → 1-(4-Ethoxy-2,3-difluorophenyl)-4-(4-ethoxy-2,3-difluorophenoxymethyl)-cyclohexane

HRID 1511482Notes

Reaction equation

HRID 1511482 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[C:6]([F:11])[C:5]=1[F:12])[CH3:2].P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl[CH2:22][CH:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH3:37])=[C:31]([F:38])[C:30]=2[F:39])[CH2:25][CH2:24]1>CN(C=O)C>[CH2:36]([O:35][C:32]1[CH:33]=[CH:34][C:29]([CH:26]2[CH2:27][CH2:28][CH:23]([CH2:22][O:10][C:7]3[CH:8]=[CH:9][C:4]([O:3][CH2:1][CH3:2])=[C:5]([F:12])[C:6]=3[F:11])[CH2:24][CH2:25]2)=[C:30]([F:39])[C:31]=1[F:38])[CH3:37]

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 144957634-Ethoxy-2,3-difluorophenolHCID 580586684-Chloromethyl-(4-ethoxy-2,3-difluorophenyl)-cyclohexane

Product 1

HCID 669624851-(4-Ethoxy-2,3-difluorophenyl)-4-(4-ethoxy-2,3-difluorophenoxymethyl)-cyclohexaneYield 49.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

4-Ethoxy-2,3-difluorophenol (6) (2.2 g) and tripotassium phosphate (K3PO4) (11.0 g) were added to DMF (100 ml) under a nitrogen atmosphere, and the stirring was continued at 70° C. The compound (20) (3.0 g) was added thereto, and the stirring was continued at 70° C. for 7 hours. After the reaction mixture obtained had been cooled to 30° C. and separated from the solid by filtration, toluene (100 ml) and water (100 ml) were added thereto and mixed. The mixture was then allowed to separate into organic and aqueous phases. The extraction into an organic phase was carried out. The organic phase obtained was washed with brine and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off, and the residue obtained was purified by means of column chromatography (silica gel/toluene=1/2 by volume). The product was further purified by means of recrystallization (Solmix A-11: heptane=1:2 by volume), giving 2.2 g of 1-(4-ethoxy-2,3-difluorophenyl)-4-(4-ethoxy-2,3-difluorophenoxymethyl)-cyclohexane (No. 828). The yield based on the compound (20) was 74.0%.

Workup

  1. customwas continued at 70° C
  2. customAfter the reaction mixture obtained
  3. customseparated from the solid by filtration, toluene (100 ml) and water (100 ml)
  4. additionwere added
  5. additionmixed
  6. customto separate into organic and aqueous phases
  7. extractionThe extraction into an organic phase
  8. customThe organic phase obtained
  9. washwas washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. distillationThen, the solvent was distilled off
  12. customthe residue obtained
  13. customwas purified by means of column chromatography (silica gel/toluene=1/2 by volume)
  14. customThe product was further purified by means of recrystallization (Solmix A-11: heptane=1:2 by volume)

Sources & evidence

ORD record
ord-ad66107672f441f194f23e7ba2397295
Source dataset
uspto-grants-2012_07
Patent number
US08216489B2

Reaction notes

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