Potassium Phosphate, Tribasic → HCID 68484956, compound

HRID 1191576Notes

Reaction equation

HRID 1191576 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[CH:15]1[C:20](=[O:21])[C:19]([CH3:23])([CH3:22])[O:18][C:17]([CH3:25])([CH3:24])[C:16]1=[O:26].[CH:27]1(B(O)O)[CH2:29][CH2:28]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[Cl:14][C:11]1[CH:10]=[CH:9][C:8]([C:5]2[CH:6]=[CH:7][C:2]([CH:27]3[CH2:29][CH2:28]3)=[C:3]([CH:15]3[C:16](=[O:26])[C:17]([CH3:24])([CH3:25])[O:18][C:19]([CH3:22])([CH3:23])[C:20]3=[O:21])[CH:4]=2)=[CH:13][CH:12]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 49787146HCID 49787146, compound

Product 1

HCID 68484956HCID 68484956, compoundYield 3.1%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 4-(4-bromo-4′-chlorobiphenyl-3-yl)-2,2,6,6-tetramethylpyran-3,5-dione (0.390 g, 0.90 mmol), cyclopropylboronic acid (0.100 g, 1.16 mmol), potassium phosphate (0.665 g, 3.14 mmol) and tricyclohexylphosphine (0.025 g, 0.09 mmol) in a mixed solvent system of toluene (4 ml) and distilled water (0.2 ml) is added palladium acetate (0.010 g, 0.044 mmol). This mixture is then heated at 100° C. overnight. After cooling to room temperature the solution is diluted with ethyl acetate and distilled water, then filtered through diatomaceous earth (additional washing with ethyl acetate/distilled water). The aqueous phase is acidified with 2M aqueous hydrochloric acid to pH3, then the organic phase is separated and the aqueous phase extracted again with ethyl acetate (×2). All organic fractions are combined, washed with brine, then dried over anhydrous magnesium sulfate and filtered. After concentration in vacuo the crude oil is purified by preparative reverse phase HPLC then triturated with hexanes to afford 4-(4′-chloro-4-cyclopropylbiphenyl-3-yl)-2,2,6,6-tetramethylpyran-3,5-dione (0.011 g) as a white solid.

Workup

  1. temperatureAfter cooling to room temperature the solution
  2. distillationdistilled water
  3. filtrationfiltered through diatomaceous earth (additional washing with ethyl acetate/distilled water)
  4. customthe organic phase is separated
  5. extractionthe aqueous phase extracted again with ethyl acetate (×2)
  6. washwashed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationAfter concentration in vacuo the crude oil
  10. customis purified by preparative reverse phase HPLC
  11. customthen triturated with hexanes

Sources & evidence

ORD record
ord-458e376ee6a84ae3b186468e25124e63
Source dataset
uspto-grants-2014_03
Patent number
US08680012B2

Reaction notes

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