Sodium Iodide → 4-((4-Bromo-3-chlorophenoxy)methyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)-isoxazole

HRID 2280852Notes

Reaction equation

HRID 2280852 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=3[Cl:16])[C:5]=2[CH2:17][OH:18])[CH2:3][CH2:2]1.O=S(Cl)Cl.[Br:23][C:24]1[CH:29]=[CH:28][C:27](O)=[CH:26][C:25]=1[Cl:31].C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>C(Cl)Cl.O>[Br:23][C:24]1[CH:29]=[CH:28][C:27]([O:18][CH2:17][C:5]2[C:6]([C:9]3[C:10]([Cl:16])=[CH:11][CH:12]=[CH:13][C:14]=3[Cl:15])=[N:7][O:8][C:4]=2[CH:1]2[CH2:3][CH2:2]2)=[CH:26][C:25]=1[Cl:31]

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 70181824-Bromo-3-chlorophenolHCID 45790382(5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methanol

Product 1

HCID 712054084-((4-Bromo-3-chlorophenoxy)methyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)-isoxazoleYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methanol (13 g, 45.8 mmol) in CH2Cl2 (DCM) (200 mL) was added dropwise SOCl2 (40 mL, 336 mmol). The resulting mixture was stirred at rt for 2 h and the solvents were removed under reduced pressure. The residue was dissolved in N,N-dimethylformamide (DMF) (200 ml) and 4-bromo-3-chlorophenol (9.7 g, 47 mmol), K2CO3 (40 g, 290 mmol) and NaI (12 g, 80 mmol) were added to this solution. The mixture was stirred at 60° C. overnight, then cooled to rt, diluted with water (1000 mL) and extracted with ethyl acetate (EA) (500 mL×3). The combined organic phases were washed with brine (500 mL×3), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (CC) to give the title compound 1a (19 g, 88%) as a white solid.

Workup

  1. customthe solvents were removed under reduced pressure
  2. dissolutionThe residue was dissolved in N,N-dimethylformamide (DMF) (200 ml)
  3. stirringThe mixture was stirred at 60° C. overnight
  4. temperaturecooled to rt
  5. extractionextracted with ethyl acetate (EA) (500 mL×3)
  6. washThe combined organic phases were washed with brine (500 mL×3)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography on silica gel (CC)

Sources & evidence

ORD record
ord-523b71ca8969493d9ca32ea3f5ab7718
Source dataset
uspto-grants-2015_09
Patent number
US09139539B2

Reaction notes

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