Potassium Phosphate, Tribasic → 3-(4'-Chloro-4-ethyl-2'-fluorobiphen-3-yl)-6,6-dimethylbicyclo[3.1.1]-heptane-2,4-dione

HRID 72302Notes

Reaction equation

HRID 72302 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=2[F:17])[CH:5]=[CH:6][C:7]=1[CH2:8][CH3:9].[CH3:18][C:19]1([CH3:28])[CH:24]2[CH2:25][CH:20]1[C:21](=[O:27])[CH2:22][C:23]2=[O:26].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([C:4]2[CH:5]=[CH:6][C:7]([CH2:8][CH3:9])=[C:2]([CH:22]3[C:21](=[O:27])[CH:20]4[CH2:25][CH:24]([C:19]4([CH3:18])[CH3:28])[C:23]3=[O:26])[CH:3]=2)=[C:11]([F:17])[CH:12]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 585864606,6-Dimethylbicyclo[3.1.1]heptane-2,4-dioneHCID 59450507HCID 59450507, compound

Product 1

HCID 914900983-(4'-Chloro-4-ethyl-2'-fluorobiphen-3-yl)-6,6-dimethylbicyclo[3.1.1]-heptane-2,4-dione

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
160 °C

Procedure

3-Bromo-4′-chloro-4-ethyl-2′-fluorobiphenyl (0.213 g, 0.68 mmol) is added to a mixture of 6,6-dimethylbicyclo[3.1.1]heptane-2,4-dione (0.124 g, 0.81 mmol), powdered potassium phosphate (0.316 g, 1.49 mmol), palladium (II) acetate (0.008 g, 0.034 mmol) and (2-dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (0.024 g, 0.051 mmol) in degassed 1,2-(2.5 ml) and the mixture is stirred and heated to 160° C. for 1 hour under microwave irradiation. The mixture is cooled to room temperature, diluted with ethyl acetate and washed with 2 M aqueous hydrochloric acid. The organic phase is washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure. The residue is taken up in N,N-dimethylformamide (2 ml) and purified by preparative reverse-phase HPLC. Fractions containing the desired product are taken up in ethyl acetate and washed with brine, dried over anhydrous magnesium sulfate, filtered and the fitrate is evaporated under reduced pressure to give 3-(4′-chloro-4-ethyl-2′-fluorobiphen-3-yl)-6,6-dimethylbicyclo[3.1.1]-heptane-2,4-dione.

Workup

  1. customin degassed 1,2-(2.5 ml)
  2. temperatureThe mixture is cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washwashed with 2 M aqueous hydrochloric acid
  5. washThe organic phase is washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customthe filtrate is evaporated under reduced pressure
  9. custompurified by preparative reverse-phase HPLC
  10. additionFractions containing the desired product
  11. washwashed with brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. customthe fitrate is evaporated under reduced pressure

Sources & evidence

ORD record
ord-fd331156665c40928a3f203119d77b01
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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