1,4-Dioxane → HCID 90101207, compound

HRID 627505Notes

Reaction equation

HRID 627505 reaction equation
O1CCOCC1.[Cl:7][C:8]1[C:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:16]([Cl:24])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH:25]([C:27]3[C:28]([CH3:33])=[N:29][O:30][C:31]=3[CH3:32])[OH:26])[CH:14]=2)[N:9]=1>C(Cl)Cl.[O-2].[O-2].[Mn+4]>[Cl:7][C:8]1[C:17]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[C:16]([Cl:24])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:25]([C:27]3[C:28]([CH3:33])=[N:29][O:30][C:31]=3[CH3:32])=[O:26])[CH:14]=2)[N:9]=1

Participants

5

Reactant 2

HCID 312751,4-DioxaneHCID 90101668HCID 90101668, compound

Product 1

HCID 90101207HCID 90101207, compound

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

THF (5 mL) was added to a mixture of 6-bromo-2,4-dichloro-3-phenylquinoline (363 mg, 1.03 mmol, Intermediate 1, step c) and 3,5-dimethylisoxazole-4-carbaldehyde (180 mg, 1.44 mmol) under a nitrogen atmosphere. The resulting colorless solution was cooled in a dry ice/acetone bath. n-BuLi (1.6 M in hexane, 0.771 mL, 1.23 mmol) was added dropwise and the mixture was stirred at −78° C. for 30 min, then moved to an ice bath and stirred for 30 min. The reaction was quenched by addition of saturated aqueous NH4Cl and was diluted with water. The mixture was extracted three times with EtOAc. The organic phase was dried (Na2SO4), filtered, and concentrated to afford crude (2,4-dichloro-3-phenylquinolin-6-yl)(3,5-dimethylisoxazol-4-yl)methanol which was used without further purification in the next step. 1,4-dioxane (7.5 mL) and manganese (IV) dioxide (447 mg, 5.14 mmol) were added to the crude alcohol from the prior step. The resulting black suspension was heated in a 100° C. oil bath in a sealed tube overnight. The mixture was allowed to cool, was diluted with DCM, and was filtered through Celite®. The filtrate was concentrated and the residue was purified by flash column chromatography—(silica gel, 3-15% EtOAc-heptane) to isolate the title compound.

Workup

  1. customwas used without further purification in the next step
  2. temperatureto cool
  3. filtrationwas filtered through Celite®
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by flash column chromatography—(silica gel, 3-15% EtOAc-heptane)

Sources & evidence

ORD record
ord-7b9d4cd3790f448ead1f6ea4c5d59b4b
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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