P-Chloroacetophenone → HCID 58573757, compound

HRID 932260Notes

Reaction equation

HRID 932260 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.Br[C:12]1[CH:13]=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=1.CC([O-])(C)C.[Na+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>C1COCC1.Cl.C(O[Pd]OC(=O)C)(=O)C.CCOCC.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH2:9][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=2)=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 7467P-ChloroacetophenoneHCID 6062563-Bromo-5-chloropyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxide

Product 1

HCID 58573757HCID 58573757, compound

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

1-(4-chlorophenyl)ethanone (17.22 ml, 133 mmol) was added to an ice cold solution of 3-bromo-5-chloropyridine (24.3 g, 126 mmol) and sodium 2-methylpropan-2-olate (30.3 g, 316 mmol) in THF (158 ml) under an argon atmosphere. (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.731 g, 1.263 mmol) and diacetoxypalladium (0.283 g, 1.263 mmol) were then added and the solution was heated to 70° C. for 1.5 hours. The solution was cooled to rt and diluted with ice, 2N HCl (95 mL) followed by EtOAc (300 ml). The layers were partitioned and the aqueous layer was washed with EtOAc (2×100 ml). The organics were washed with brine, dried over Na2SO4, filtered, and concentrated. The residue obtained was enriched on a silica gel column. The fractions containing the product were combined and concentrated. To the residue obtained was added 130 ml of Et2O and the suspension was heated to a reflux in a water bath. The suspension was then cooled in an ice bath. The solids were collected by filtration to provide the title compound.

Workup

  1. temperatureThe solution was cooled to rt
  2. customThe layers were partitioned
  3. washthe aqueous layer was washed with EtOAc (2×100 ml)
  4. washThe organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue obtained
  9. additionThe fractions containing the product
  10. concentrationconcentrated
  11. customTo the residue obtained
  12. temperaturethe suspension was heated to
  13. temperaturea reflux in a water bath
  14. temperatureThe suspension was then cooled in an ice bath
  15. filtrationThe solids were collected by filtration

Sources & evidence

ORD record
ord-74a44b3c387d4afe87270b95f1c1383e
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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