Potassium Carbonate → Methyl 2-(5,5-dimethyl-1-cyclopenten-1-yl)-2',5-difluoro-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

HRID 1662429Notes

Reaction equation

HRID 1662429 reaction equation
[CH3:1][C:2]1([CH3:26])[C:6]([C:7]2[C:8](OS(C(F)(F)F)(=O)=O)=[CH:9][C:10]([F:17])=[C:11]([CH:16]=2)[C:12]([O:14][CH3:15])=[O:13])=[CH:5][CH2:4][CH2:3]1.[F:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.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:2]1([CH3:1])[C:6]([C:7]2[CH:16]=[C:11]([C:12]([O:14][CH3:15])=[O:13])[C:10]([F:17])=[CH:9][C:8]=2[C:29]2[CH:30]=[C:31]([O:34][CH3:35])[CH:32]=[CH:33][C:28]=2[F:27])=[CH:5][CH2:4][CH2:3]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 57706168Methyl 5-(5,5-dimethylcyclopent-1-enyl)-2-fluoro-4-(trifluoromethylsulfonyloxy)benzoate

Product 1

HCID 57706663Methyl 2-(5,5-dimethyl-1-cyclopenten-1-yl)-2',5-difluoro-5'-(methyloxy)-1,1'-biphenyl-4-carboxylateYield 93%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 66.43F (1.05 g, 2.65 mmol) in DMF (5 mL) at 23° C. was added 2-fluoro-5-methoxyphenylboronic acid (0.90 g, 5.32 mmol) (commercially available from Aldrich) and potassium carbonate (1.10 g, 7.96 mmol) followed by tetrakis(triphenylphosphine)palladium (0.31 g, 0.27 mmol). The mixture was heated to 90° C. After 17 hours, the mixture was cooled to room temperature and then diluted with water. After extracting three times with EtOAc, the mixture was concentrated in vacuo and then purified on silica gel (0%-10% EtOAc/hexane) to give 66.43G as a clear oil that was used without further purification (0.92 g, 93% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.79 (1H, d, J=7.4 Hz), 7.13 (1H, d, J=11.3 Hz), 6.99 (1H, t, J=9.0 Hz), 6.84 (1H, dt, J=8.7, 3.7 Hz), 6.78 (1H, dd, J=5.9, 3.1 Hz), 5.55 (1H, s), 3.96 (3H, s), 3.79 (3H, s), 2.27 (2H, td, J=7.1, 2.5 Hz), 1.67 (2H, t, J=7.0 Hz), 0.84 (6H, s).

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. extractionAfter extracting three times with EtOAc
  3. concentrationthe mixture was concentrated in vacuo
  4. custompurified on silica gel (0%-10% EtOAc/hexane)

Sources & evidence

ORD record
ord-ad73ad9b92544b67b473b32123189264
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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