Hydrogen Peroxide → 5-(3-bromo-2-fluoro-6-hydroxy-phenoxy)-N,N'-di-tert-butyl-isophthalamide

HRID 602592Notes

Reaction equation

HRID 602592 reaction equation
OO.FC(F)(F)C(OO)=[O:6].[Br:11][C:12]1[C:13]([F:41])=[C:14]([C:36](C=O)=[CH:37][CH:38]=1)[O:15][C:16]1[CH:17]=[C:18]([C:29]([NH:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH:19]=[C:20]([CH:28]=1)[C:21]([NH:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O[Li].O>C(Cl)Cl.O.CCOC(C)=O>[Br:11][C:12]1[C:13]([F:41])=[C:14]([C:36]([OH:6])=[CH:37][CH:38]=1)[O:15][C:16]1[CH:17]=[C:18]([C:29]([NH:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[CH:19]=[C:20]([CH:28]=1)[C:21]([NH:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22]

Participants

9

Reactant 5

HCID 784Hydrogen PeroxideHCID 62657Potassium Phosphate, TribasicHCID 168937Lithium hydroxide, monohydrateHCID 10290812Trifluoroperacetic acidHCID 866236405-(3-bromo-2-fluoro-6-formyl-phenoxy)-N,N'-di-tert-butyl-isophthalamide

Product 1

HCID 691015735-(3-bromo-2-fluoro-6-hydroxy-phenoxy)-N,N'-di-tert-butyl-isophthalamideYield 75%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

step 5a—Trifluoroacetic anhydride (1.3 mL, 12 eq.) and H2O2 (0.24 mL, 2.5 eq.) were combined at 0° C. and stirred for 2 h. The mixture containing trifluoroperacetic acid was added to a mixture of 5-(3-bromo-2-fluoro-6-formyl-phenoxy)-N,N′-di-tert-butyl-isophthalamide from step 4 (0.4 g, 0.81 mmol) and potassium phosphate (2.2 g, 20 eq.) in DCM at 0° C. and the reaction mixture stirred for 5 h. The reaction mixture was diluted with DCM and washed sequentially with sodium bisulfite and brine. The solution containing the formate ester was concentrated in vacuo and the residue was dissolved in THF (4 mL) and a solution of LiOH.H2O (0.43 g, 3 eq.) in H2O (1 mL) was added to the reaction mixture and stirred for 5 h. The reaction mixture was diluted with EtOAc and washed with HCl (aqueous), water, and brine. The organic phase was dried (Na2SO4), filtered and evaporated to afford 0.300 g (75%) of 5-(3-bromo-2-fluoro-6-hydroxy-phenoxy)-N,N′-di-tert-butyl-isophthalamide (D-2b, Ar=3,5-di-tert-butyl-dicarboxamido-phenyl).

Workup

  1. customwere combined at 0° C.
  2. stirringthe reaction mixture stirred for 5 h
  3. washwashed sequentially with sodium bisulfite and brine
  4. additionThe solution containing the formate ester
  5. concentrationwas concentrated in vacuo
  6. dissolutionthe residue was dissolved in THF (4 mL)
  7. stirringstirred for 5 h
  8. washwashed with HCl (aqueous), water, and brine
  9. dry with materialThe organic phase was dried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-ab9188136d9d4418b4101b61fa346cac
Source dataset
uspto-grants-2011_03
Patent number
US07906540B2

Reaction notes

Loading…