Potassium Carbonate → 5-(Tert-butyl)-2-hydroxy-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carbaldehyde

HRID 929555Notes

Reaction equation

HRID 929555 reaction equation
Br[C:2]1[C:3]([OH:14])=[C:4]([CH:7]=[C:8]([C:10]([CH3:13])([CH3:12])[CH3:11])[CH:9]=1)[CH:5]=[O:6].C(=O)([O-])[O-].[K+].[K+].[F:21][C:22]([F:34])([F:33])[O:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1>COCCOC.O.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>[C:10]([C:8]1[CH:7]=[C:4]([CH:5]=[O:6])[C:3]([OH:14])=[C:2]([C:27]2[CH:26]=[CH:25][C:24]([O:23][C:22]([F:21])([F:33])[F:34])=[CH:29][CH:28]=2)[CH:9]=1)([CH3:13])([CH3:12])[CH3:11]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 71720963-Bromo-5-tert-butyl-2-hydroxybenzaldehyde2×

Product 1

HCID 867187195-(Tert-butyl)-2-hydroxy-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carbaldehydeYield 85.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 3-bromo-5-(tert-butyl)-2-hydroxybenzaldehyde (Intermediate 4) (4 g, 15.56 mmol) in DME (30 mL) and water (10 mL) was purged with nitrogen for 15 minutes. Potassium carbonate (3.2 g, 23.15 mmol), 4-trifluoromethoxybenzeneboronic acid (3.2 g, 15.54 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.78 g, 0.675 mmol) were added and the reaction mixture heated to reflux under nitrogen overnight. The cooled reaction mixture was then filtered through celite washing through with diethyl ether. The filtrate was dried (MgSO4), filtered and concentrated under reduced pressure. The product was purified using flash chromatography on silica eluting with a solvent gradient of 0 to 100% ethyl acetate in hexanes to give 5-(tert-butyl)-2-hydroxy-4′-(trifluoromethoxy)-[1,1′-biphenyl]-3-carbaldehyde (4.5 g, 85%).

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureto reflux under nitrogen overnight
  3. customThe cooled reaction mixture
  4. filtrationwas then filtered through celite
  5. washwashing through with diethyl ether
  6. dry with materialThe filtrate was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe product was purified

Sources & evidence

ORD record
ord-46b39dbc1faa4ea2a0df75ff3eaee4ad
Source dataset
uspto-grants-2016_03
Patent number
US09296696B2

Reaction notes

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