Water → 7-chloro-3-cyclopropyl-4-(4-fluorophenyl)-2,2-dimethyl-2H-chromen

HRID 2380894Notes

Reaction equation

HRID 2380894 reaction equation
Br[C:2]1[C:3]([CH3:21])([CH3:20])[O:4][C:5]2[C:10]([C:11]=1[C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)=[CH:9][CH:8]=[C:7]([Cl:19])[CH:6]=2.[CH:22]1(B(O)O)[CH2:24][CH2:23]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.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>[Cl:19][C:7]1[CH:6]=[C:5]2[C:10]([C:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)=[C:2]([CH:22]3[CH2:24][CH2:23]3)[C:3]([CH3:21])([CH3:20])[O:4]2)=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 59443055HCID 59443055, compound

Product 1

HCID 594430267-chloro-3-cyclopropyl-4-(4-fluorophenyl)-2,2-dimethyl-2H-chromen

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3-bromo-7-chloro-4-(4-fluorophenyl)-2,2-dimethyl-2H-chromen (a compound obtained in Reference Example 8(1); 200 mg), cyclopropylboronic acid (100 mg), potassium phosphate (410 mg) and tetrakis(triphenylphosphine)palladium(0) (65 mg) in dioxane (5 mL) was heated under reflux for 23 hours. After cooling, to the reaction solution was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and filtered through a column of porous diatomite (Chem Elut), and the filtrate was concentrated in vacuo. The resultant residue was purified by column chromatography on silica gel (Solvent: n-hexane/chloroform=100/0 to 95/5) to give the titled compound (114 mg) as a colorless viscous oil.

Workup

  1. customobtained in Reference Example 8(1)
  2. temperatureunder reflux for 23 hours
  3. temperatureAfter cooling, to the reaction solution
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. filtrationfiltered through a column of porous diatomite (Chem Elut)
  7. concentrationthe filtrate was concentrated in vacuo
  8. customThe resultant residue was purified by column chromatography on silica gel (Solvent: n-hexane/chloroform=100/0 to 95/5)

Sources & evidence

ORD record
ord-81814bde635a463fba271d45438e23e3
Source dataset
uspto-grants-2012_09
Patent number
US08258131B2

Reaction notes

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