Dimethylformamide → Methyl 2'-fluoro-5'-(methyloxy)-2-(2-methylpropyl)-1,1'-biphenyl-4-carboxylate

HRID 1662405Notes

Reaction equation

HRID 1662405 reaction equation
[CH3:1][CH:2]([CH3:22])[CH2:3][C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][C:13]=1OS(C(F)(F)F)(=O)=O)[C:7]([O:9][CH3:10])=[O:8].CN(C=O)C.[F:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][C:30]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>[Cl-].[Na+].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>[F:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][C:30]=1[C:13]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][C:4]=1[CH2:3][CH:2]([CH3:1])[CH3:22]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 57705615Methyl 3-(2-methylpropyl)-4-(((trifluoromethyl)sulfonyl)oxy)benzoate

Product 1

HCID 57706197Methyl 2'-fluoro-5'-(methyloxy)-2-(2-methylpropyl)-1,1'-biphenyl-4-carboxylateYield 79%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 66.20D (0.400 g, 1.2 mmol) in DMF (4.00 mL, 52 mmol) at 23° C. was added 2-fluoro-5-methoxyphenylboronic acid (0.40 g, 2.4 mmol) (commercially available from Aldrich), potassium carbonate (0.49 g, 3.5 mmol), and then tetrakis(triphenylphosphine)palladium (0.14 g, 0.12 mmol). The mixture was heated to 90° C. and stirred for 22 hours. The mixture was cooled to room temperature, diluted with brine, and extracted three times with EtOAc. After drying over anhydrous magnesium sulfate and filtering, the organic solvent was removed under reduced pressure and the product was then purified on silica gel (0-10% EtOAc in hexanes) to yield 66.20E as a colorless oil (0.293 g, 79% yield).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted three times with EtOAc
  3. dry with materialAfter drying over anhydrous magnesium sulfate
  4. filtrationfiltering
  5. customthe organic solvent was removed under reduced pressure
  6. customthe product was then purified on silica gel (0-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2df8190c84434f1f85eb84b8d00a36b3
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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