Trifluoroacetic acid → (3-{[3-Cyano-5-(methyloxy)phenyl]oxy}-2-fluoro-4-nitrophenyl)acetic acid

HRID 1875242Notes

Reaction equation

HRID 1875242 reaction equation
CC([O:5][C:6](=[O:36])[CH:7]([C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17]([O:24][C:25]2[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[C:27]([C:33]#[N:34])[CH:26]=2)[C:16]=1[F:35])C(OC(C)(C)C)=O)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:33]([C:27]1[CH:26]=[C:25]([O:24][C:17]2[C:16]([F:35])=[C:15]([CH2:7][C:6]([OH:36])=[O:5])[CH:20]=[CH:19][C:18]=2[N+:21]([O-:23])=[O:22])[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=1)#[N:34]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68724212Bis(1,1-dimethylethyl)(3-{[3-cyano-5-(methyloxy)phenyl]oxy}-2-fluoro-4-nitrophenyl)propanedioate

Product 1

HCID 68725114(3-{[3-Cyano-5-(methyloxy)phenyl]oxy}-2-fluoro-4-nitrophenyl)acetic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of bis(1,1-dimethylethyl)(3-{[3-cyano-5-(methyloxy)phenyl]oxy}-2-fluoro-4-nitrophenyl)propanedioate (12.79 g, 25.5 mmol) in CH2Cl2 (25 ml) and TFA (25 ml, 324 mmol) was stirred at RT overnight. The reaction mixture was evaporated and the residue was dissolved in water and EtOAc. The aqueous layer was extracted with EtOAc. The organic layers were dried (Na2SO4), filtered, evaporated to give (3-{[3-cyano-5-(methyloxy)phenyl]oxy}-2-fluoro-4-nitrophenyl)acetic acid as a brown solid that was used without further purification. A solution of the above acid and Cu2O (0.74 g, 5.2 mmol) in acetonitrile (50 mL) was heated under reflux overnight. The reaction mixture was brought to RT, filtered through celite, evaporated and purified by silica gel chromatography (0-25% EtOAc/hexanes) to afford the title compound (2.20 g, 29%) as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.77 (dd, J=8.61, 1.56 Hz, 1H) 6.85-6.90 (m, 1H) 6.73 (t, J=2.06 Hz, 1H) 6.65 (d, J=0.73 Hz, 1H) 3.80 (s, 3H) 2.39 (d, J=2.20 Hz, 3H).

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutionthe residue was dissolved in water
  3. extractionThe aqueous layer was extracted with EtOAc
  4. dry with materialThe organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-8fe12d85dc034a2595491573f62d14b4
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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