Potassium Phosphate, Tribasic → 5-(4-Fluorophenyl)-7-isopropyl-4-oxo-3,4-dihydrospiro[chromen-2,1'-cyclobutane]-6-carbaldehyde

HRID 1516716Notes

Reaction equation

HRID 1516716 reaction equation
FC(F)(F)S(O[C:7]1[C:19]([CH:20]=[O:21])=[C:18]([CH:22]([CH3:24])[CH3:23])[CH:17]=[C:16]2[C:8]=1[C:9](=[O:25])[CH2:10][C:11]1([O:15]2)[CH2:14][CH2:13][CH2:12]1)(=O)=O.[F:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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>[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:7]2[C:19]([CH:20]=[O:21])=[C:18]([CH:22]([CH3:24])[CH3:23])[CH:17]=[C:16]3[C:8]=2[C:9](=[O:25])[CH2:10][C:11]2([O:15]3)[CH2:14][CH2:13][CH2:12]2)=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 58002941HCID 58002941, compound

Product 1

HCID 580030415-(4-Fluorophenyl)-7-isopropyl-4-oxo-3,4-dihydrospiro[chromen-2,1'-cyclobutane]-6-carbaldehyde

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

Under argon, 4.00 g (9.84 mmol) of 6-formyl-7-isopropyl-4-oxo-3,4-dihydrospiro[chromen-2,1′-cyclobutan]-5-yl trifluoromethanesulfonate (Example 50A), 1.79 g (12.8 mmol) of 4-fluorophenyl-boronic acid, 3.55 g (16.73 mmol) of tripotassium phosphate and 1.25 g (1.08 mmol) of tetrakis(triphenylphosphine)palladium(0) are initially charged and the apparatus is flushed by repeated evacuation and venting with argon. 100 ml of abs. dioxane are then added, the apparatus is closed and the mixture is heated under reflux. After stirring overnight, the mixture is cooled and filtered through a layer of silica gel, the filter cake is washed thoroughly with ethyl acetate and the filtrate is concentrated. The residue is adsorbed on silica gel and chromatographed on a silica gel column (mobile phase: cyclohexane→cyclohexane/ethyl acetate 25:1). The crude product obtained is triturated with hot petroleum ether and cooled slowly, and the precipitate is filtered off with suction. This gives 3.2 g of the target compound in a purity of about 90%.

Workup

  1. customthe apparatus is flushed
  2. additiondioxane are then added
  3. customthe apparatus is closed
  4. temperaturethe mixture is heated
  5. temperatureunder reflux
  6. temperaturethe mixture is cooled
  7. filtrationfiltered through a layer of silica gel
  8. washthe filter cake is washed thoroughly with ethyl acetate
  9. concentrationthe filtrate is concentrated
  10. customchromatographed on a silica gel column (mobile phase: cyclohexane→cyclohexane/ethyl acetate 25:1)

Sources & evidence

ORD record
ord-8a594ce884de4428a98433ead5493696
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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