Dimethylformamide → [1,1′-Biphenyl]-4-carboxylic acid, 2-(6,6-dimethyl-1-cyclohexen-1-yl)-2′-fluoro-5′-methoxy-, methyl ester

HRID 1662406Notes

Reaction equation

HRID 1662406 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][C:11]=1I.CN(C=O)C.[CH3:26][C:27]1([CH3:42])[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH2:30][CH2:29][CH2:28]1.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>[CH3:26][C:27]1([CH3:42])[C:28]([C:11]2[CH:12]=[C:13]([C:16]([O:18][CH3:19])=[O:17])[CH:14]=[CH:15][C:10]=2[C:3]2[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=2[F:1])=[CH:29][CH2:30][CH2:31][CH2:32]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 57467612HCID 57467612, compoundHCID 57705628Methyl 2'-fluoro-2-iodo-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

Product 1

HCID 57706936[1,1′-Biphenyl]-4-carboxylic acid, 2-(6,6-dimethyl-1-cyclohexen-1-yl)-2′-fluoro-5′-methoxy-, methyl esterYield 48.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 66.15D (0.750 g, 1.9 mmol) in DMF (4.00 mL, 52 mmol) at 23° C. was added 66.21B (0.92 g, 3.9 mmol), potassium carbonate (0.81 g, 5.8 mmol), and then tetrakis(triphenylphosphine)palladium (0.22 g, 0.19 mmol). The mixture was heated to 90° C. and stirred for 24 hours. The reaction was then 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 66.21C as a colorless oil (0.34 g, 48% yield).

Workup

  1. temperatureThe reaction was then 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-bd2a261bad154a12925ca2809be76ad7
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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