Sodium Carbonate → 2,4'-Difluoro-3-hydroxy-[1,1'-biphenyl]-4-carbaldehyde

HRID 531097Notes

Reaction equation

HRID 531097 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2C2C(OC)=CC=CC=2OC)C2CCCCC2)CCCCC1.Br[C:47]1[CH:54]=[CH:53][C:50]([CH:51]=[O:52])=[C:49]([OH:55])[C:48]=1[F:56]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:56][C:48]1[C:49]([OH:55])=[C:50]([CH:51]=[O:52])[CH:53]=[CH:54][C:47]=1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 978894044-Bromo-3-fluoro-2-hydroxybenzaldehyde

Product 1

HCID 904239512,4'-Difluoro-3-hydroxy-[1,1'-biphenyl]-4-carbaldehydeYield 55.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

(4-Fluorophenyl)boronic acid (33.2 g), 2M aqueous sodium carbonate solution (237 mL), palladium (II) acetate (2.49 g) and dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (9.74 g) were added to a solution of 4-bromo-3-fluoro-2-hydroxybenzaldehyde (34.6 g) in DME (350 mL) at room temperature. The mixture was stirred at 100° C. under argon atmosphere for 16 hours. The mixture was cooled to room temperature. Water (700 mL) was added to the reaction mixture. The mixture was concentrated in vacuo to remove DME. The precipitate was collected by filtration and washed with water. The aqueous filtrate was set aside for further purification. Then the solid was washed with ethyl acetate. The solid was added to a mixture of ethyl acetate and 1M hydrochloric acid. The mixture was stirred at room temperature for 1 hour and filtrated through celite. The filtrate was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (20.6 g).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationThe mixture was concentrated in vacuo
  3. customto remove DME
  4. filtrationThe precipitate was collected by filtration
  5. washwashed with water
  6. customThe aqueous filtrate was set aside for further purification
  7. washThen the solid was washed with ethyl acetate
  8. additionThe solid was added to a mixture of ethyl acetate and 1M hydrochloric acid
  9. stirringThe mixture was stirred at room temperature for 1 hour
  10. filtrationfiltrated through celite
  11. extractionThe filtrate was extracted with ethyl acetate
  12. customThe organic layer was separated
  13. washwashed with water and brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f64b003c45ab4260a6551231b73749f9
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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