Toluene → 4-Ethoxy-3,3'-difluoro-[1,1'-biphenyl]-2,2'-dicarboaldehyde

HRID 718502Notes

Reaction equation

HRID 718502 reaction equation
Cl[C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[CH:4]=[O:5].[CH2:11]([O:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[C:16]([CH:23]=[O:24])[C:15]=1[F:25])[CH3:12].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].O.C(O)C>[CH2:11]([O:13][C:14]1[C:15]([F:25])=[C:16]([CH:23]=[O:24])[C:17]([C:2]2[C:3]([CH:4]=[O:5])=[C:6]([F:10])[CH:7]=[CH:8][CH:9]=2)=[CH:18][CH:19]=1)[CH3:12]

Participants

8

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 678472-Chloro-6-fluorobenzaldehydeHCID 469186104-Ethoxy-3-fluoro-2-formylphenylboronic acid

Product 1

HCID 866960744-Ethoxy-3,3'-difluoro-[1,1'-biphenyl]-2,2'-dicarboaldehydeYield 84.5%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Under a nitrogen atmosphere, a mixture of 2-chloro-6-fluorobenzaldehyde (84) (50.0 g, 315 mmol), compound (55) (73.5 g, 347 mmol), Pd-132 (made by Johnson Matthey Catalysis and Chiral Technologies) (0.223 g, 0.315 mmol), potassium carbonate (87 g, 631 mmol) and TBAB (20.33 g, 63.1 mmol) was refluxed in a toluene 500 mL)-ethanol (100 mL)-water (500 mL) solvent for 5 hours. The reaction mixture was extracted with 300 mL of toluene three times. Combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, 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-[1,1′-biphenyl]-2,2′-dicarboaldehyde (85) (77.25 g, yield 84%) was obtained.

Workup

  1. extractionThe reaction mixture was extracted with 300 mL of toluene three times
  2. washCombined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, 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-235f111e361847b19f48ec57fefcdd77
Source dataset
uspto-grants-2015_11
Patent number
US09193908B2

Reaction notes

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