Sodium Carbonate → 4-(Benzyloxy)-2'-fluoro-5'-methoxy-[1,1'-biphenyl]-3-carbaldehyde

HRID 1049439Notes

Reaction equation

HRID 1049439 reaction equation
[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:14](Br)=[CH:13][C:10]=1[CH:11]=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:14]([C:20]2[CH:21]=[C:22]([O:25][CH3:26])[CH:23]=[CH:24][C:19]=2[F:18])=[CH:13][C:10]=1[CH:11]=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 7330872-(Benzyloxy)-5-bromobenzaldehydeHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 1177599394-(Benzyloxy)-2'-fluoro-5'-methoxy-[1,1'-biphenyl]-3-carbaldehydeYield 69.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-(benzyloxy)-5-bromobenzaldehyde (5.00 g) in toluene (70 mL) were added (2-fluoro-5-methoxyphenyl)boronic acid (4.40 g), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (710 mg), tris(dibenzylideneacetone)dipalladium(0) (790 mg) and 2.0M aqueous sodium carbonate solution (25.8 mL) at room temperature, and the mixture was stirred at 100° C. for 1 hr. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (4.00 g) as orange crystals.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a164ce5263464343ab8c637bb7e3852b
Source dataset
uspto-grants-2016_07
Patent number
US09382188B2

Reaction notes

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