Toluene → 4-Ethoxy-3,3'-difluoro-4'-((4-propylcyclohexyl)methoxy)-[1,1'-biphenyl]-2,2'-dicarboaldehyde

HRID 718489Notes

Reaction equation

HRID 718489 reaction equation
Br[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([F:10])[C:5]([O:11][CH2:12][CH:13]2[CH2:18][CH2:17][CH:16]([CH2:19][CH2:20][CH3:21])[CH2:15][CH2:14]2)=[CH:4][CH:3]=1.[CH2:22]([O:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[C:27]([CH:34]=[O:35])[C:26]=1[F:36])[CH3:23].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].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.O.C(O)C>[CH2:22]([O:24][C:25]1[C:26]([F:36])=[C:27]([CH:34]=[O:35])[C:28]([C:2]2[C:7]([CH:8]=[O:9])=[C:6]([F:10])[C:5]([O:11][CH2:12][CH:13]3[CH2:18][CH2:17][CH:16]([CH2:19][CH2:20][CH3:21])[CH2:15][CH2:14]3)=[CH:4][CH:3]=2)=[CH:29][CH:30]=1)[CH3:23]

Participants

9

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 469186104-Ethoxy-3-fluoro-2-formylphenylboronic acidHCID 866960666-Bromo-2-fluoro-3-((4-propylcyclohexyl)methoxy)benzaldehyde

Product 1

HCID 866960654-Ethoxy-3,3'-difluoro-4'-((4-propylcyclohexyl)methoxy)-[1,1'-biphenyl]-2,2'-dicarboaldehydeYield 80.3%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Under a nitrogen atmosphere, a mixture of compound (62) (4.20 g, 11.76 mmol), compound (55) (2.74 g, 12.93 mmol) prepared in Example 1, tetrakis(triphenylphosphine)palladium (0.14 g, 0.121 mmol), potassium carbonate (3.25 g, 23.51 mmol) and TBAB (0.76 g, 2.351 mmol) was refluxed in a toluene (20 mL)-ethanol (10 mL)-water (50 mL) solvent for 5 hours. The reaction mixture was extracted with 20 mL of toluene three times, combined organic layers were washed with water and saturated brine, and then dried over magnesium sulfate, and a solvent was distilled off by an evaporator. The residue was purified by silica gel column chromatography, and thus 4-ethoxy-3,3′-difluoro-4′-((4-propylcyclohexyl)methoxy)-[1,1′-biphenyl]-2,2′-dicarboaldehyde (63) (4.20 g, yield 80.3%) was obtained.

Workup

  1. extractionThe reaction mixture was extracted with 20 mL of toluene three times
  2. washwere washed with water and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. distillationa solvent was distilled off by an evaporator
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d5be42ece89d433a845addaef5a9d56a
Source dataset
uspto-grants-2015_11
Patent number
US09193908B2

Reaction notes

Loading…