Potassium Fluoride → 2'-fluoro-5'-methoxy-2-(2,2,6,6-tetramethyl-3,6-dihydro-2H-pyran-4-yl)biphenyl-4-ol

HRID 1049590Notes

Reaction equation

HRID 1049590 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([O:13][Si](C(C)(C)C)(C)C)[CH:10]=[CH:9][C:8]=1[C:21]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:22]=1[F:29])(=O)=O.[CH3:32][C:33]1([CH3:50])[CH2:38][C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][C:35]([CH3:49])([CH3:48])[O:34]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[F-].[K+]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1.CO>[F:29][C:22]1[CH:23]=[CH:24][C:25]([O:27][CH3:28])=[CH:26][C:21]=1[C:8]1[CH:9]=[CH:10][C:11]([OH:13])=[CH:12][C:7]=1[C:37]1[CH2:36][C:35]([CH3:49])([CH3:48])[O:34][C:33]([CH3:50])([CH3:32])[CH:38]=1

Participants

9

Reactant 4

HCID 522689Potassium FluorideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 467380002,2,6,6-Tetramethyl-3,6-dihydro-2H-pyran-4-boronic acid pinacol esterHCID 1317360334-((Tert-butyl(dimethyl)silyl)oxy)-2'-fluoro-5'-methoxybiphenyl-2-yl trifluoromethanesulfonate

Product 1

HCID 1177600932'-fluoro-5'-methoxy-2-(2,2,6,6-tetramethyl-3,6-dihydro-2H-pyran-4-yl)biphenyl-4-olYield 41.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-((tert-butyl(dimethyl)silyl)oxy)-2′-fluoro-5′-methoxybiphenyl-2-yl trifluoromethanesulfonate (405 mg), 2,2,6,6-tetramethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (452 mg), palladium acetate (20 mg), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (83 mg), methanol (3 mL) and toluene (3 mL) was added potassium fluoride (151 mg) and, under microwave irradiation, the mixture was stirred at 100° C. for 20 min. The reaction mixture was diluted with ethyl acetate. The diluted solution was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (125 mg) as white crystals.

Workup

  1. customunder microwave irradiation
  2. washThe diluted solution was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-84ea37d28eca4c0cae1ea3a68209e9fe
Source dataset
uspto-grants-2016_07
Patent number
US09382188B2

Reaction notes

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