Phosphorus tribromide → 4-(Bromomethyl)-5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]isoxazole

HRID 1689763Notes

Reaction equation

HRID 1689763 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:19])([F:18])[F:17])[C:5]=2[CH2:20]O)[CH2:3][CH2:2]1.P(Br)(Br)[Br:23]>C(Cl)Cl>[Br:23][CH2:20][C:5]1[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][C:16]([F:19])([F:18])[F:17])=[N:7][O:8][C:4]=1[CH:1]1[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 24614Phosphorus tribromideHCID 669061975-Cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-4-isoxazolemethanol

Product 1

HCID 669060924-(Bromomethyl)-5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]isoxazoleYield 79.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (5-cyclopropyl-3-(2-trifluormethoxy-phenyl)-isoxazol-4-yl)-methanol (2.19 g, 7.32 mmol) in anhydrous methylene chloride (50 mL) at 0° C. is added PBr3 (0.83 mL, 8.7 mmol) and the mixture is stirred for 3 hours. The mixture is then poured into 100 mL of ice water and extracted with DCM (2×). The combined DCM layers are washed with brine, dried (MgSO4) and concentrated under reduced pressure to provide crude residue. The residue is purified via flash chromatography (120 g silica) eluting with a gradient of 0 to 60% ethyl acetate in heptane to provide the title compound (2.1 g, 79%) as an oil.

Workup

  1. extractionextracted with DCM (2×)
  2. washThe combined DCM layers are washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customto provide crude residue
  6. customThe residue is purified via flash chromatography (120 g silica)
  7. washeluting with a gradient of 0 to 60% ethyl acetate in heptane

Sources & evidence

ORD record
ord-9e84e084dab048989fc9b75c1dabbf71
Source dataset
uspto-grants-2012_04
Patent number
US08153624B2

Reaction notes

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