Toluene → HCID 178447849, compound

HRID 630560Notes

Reaction equation

HRID 630560 reaction equation
[F:1][C:2]1[CH:3]=[C:4](Br)[CH:5]=[C:6]([F:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[F:16][C:17]1[CH:22]=[C:21]([C@H:23]2[CH2:28][CH2:27][C@H:26]([CH2:29][CH2:30][CH3:31])[CH2:25][CH2:24]2)[CH:20]=[CH:19][C:18]=1OB(O)O.C1(C)C=CC=CC=1>C(O)C.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>[F:16][C:17]1[CH:22]=[C:21]([C@H:23]2[CH2:28][CH2:27][C@H:26]([CH2:29][CH2:30][CH3:31])[CH2:25][CH2:24]2)[CH:20]=[CH:19][C:18]=1[C:7]1[C:2]([F:1])=[CH:3][CH:4]=[CH:5][C:6]=1[F:8]

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 1363131-Bromo-3,5-difluorobenzeneHCID 178447895HCID 178447895, compound

Product 1

HCID 178447849HCID 178447849, compoundYield 75.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent2×

Conditions

Temperature
50 °C

Procedure

3,5-Difluorobromobenzene (30 g), tetrakis(triphenylphosphine)palladium (0) (1.8 g), ethanol (150 mL), and a 2 mol/L aqueous potassium carbonate solution (155 mL) were mixed with each other and heated to 50° C. A solution prepared by dissolving 2-fluoro-4-(trans-4-propylcyclohexyl)phenylboric acid (49.3 g) in ethanol (300 mL) was added thereto, and stirring was performed at 50° C. for five hours. After the temperature was decreased to room temperature by natural cooling, toluene (300 mL) was added thereto and the mixture was separated. The resulting organic layer was washed with a saturated saline solution (200 mL) twice. Anhydrous sodium sulfate was added to perform drying, and the organic solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography and recrystallized using ethanol to obtain 4-[2-fluoro-4-(trans-4-propylcyclohexyl)phenyl]-3,5-difluorobenzene (39.1 g). (2-2) The subsequent processes were performed by the same method as in Example 1 to obtain [3,5-difluoro-4-(2-fluoro-4-(trans-4-propylcyclohexyl)phenyl)phenyl]-(5,6,7-trifluoro-2-naphthyloxy)difluoromethane (20.5 g).

Workup

  1. customA solution prepared
  2. additionwas added
  3. additionwas added
  4. customthe mixture was separated
  5. washThe resulting organic layer was washed with a saturated saline solution (200 mL) twice
  6. additionAnhydrous sodium sulfate was added
  7. customto perform drying
  8. distillationthe organic solvent was distilled off under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography
  10. customrecrystallized

Sources & evidence

ORD record
ord-a4a9f0543ab044eaa977523835f452c7
Source dataset
uspto-grants-2016_04
Patent number
US09315727B2

Reaction notes

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