Potassium Carbonate → 5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[4'-fluoro-5'isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-1,3-oxazolidin-2-one

HRID 1028533

Reaction equation

HRID 1028533 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3I)[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[F:33][C:34]1[C:39]([CH:40]([CH3:42])[CH3:41])=[CH:38][C:37](B(O)O)=[C:36]([O:46][CH3:47])[CH:35]=1.C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(C)=O.O>[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:37]3[CH:38]=[C:39]([CH:40]([CH3:42])[CH3:41])[C:34]([F:33])=[CH:35][C:36]=3[O:46][CH3:47])[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 53363739(4-Fluoro-5-isopropyl-2-methoxyphenyl)boronic acidHCID 591352395-[3,5-Bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]1,3-oxazolidin-2-one

Product 1

HCID 117142705-[3,5-Bis(trifluoromethyl)phenyl]-3-{[4'-fluoro-5'isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 18366337Propan-2-one--water (1/1)Solvent

Procedure

A mixture of 5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one (60 mg; 0.103 mmol), (4-fluoro-5-isopropyl-2-methoxyphenyl)boronic acid (27 mg; 0.129 mmol), palladium acetate (7 mg; 0.0103 mmol), and potassium carbonate (36 mg; 0.257 mmol) in 5:1 acetone/water (6 mL) was heated at reflux for 1 h. Acetone was removed in vacuo and the residue was diluted with H2O (10 mL) and extracted with CH2Cl2 (3×10 mL). The combined extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (0-25% EtOAc/hexanes gradient) to afford 5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4′-fluoro-5′isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-1,3-oxazolidin-2-one as a clear glass. LCMS=624.2 (M+1)+. 1H NMR (benzene-d6, 500 MHz, 1:1 mixture of atropisomers): δ 7.60 (s, 1.5 H), 7.45 (s, 0.5 H), 7.31-7.25 (m, 3 H), 6.98-6.94 (m, 1 H), 6.87-6.82 (m, 1 H), 6.43-6.37 (m, 1 H), 4.54 (d, J=15.6 Hz, 0.5 H), 4.40-4.36 (m, 1 H), 4.47 (d, J=15.6 Hz, 0.5 H), 3.96 (d, J=15.5 Hz, 0.5 H), 3.80 (d, J=15.8 Hz, 0.5 H), 3.24-3.15 (m, 1 H), 3.02 (s, 3H), 2.62-2.58 (m, 0.5 H), 2.53-2.48 (m, 0.5 H), 2.12-2.07 (m, 0.5 H), 2.04-2.00 (m, 0.5 H) 1.22-1.11 (m, 6 H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 h
  3. customAcetone was removed in vacuo
  4. additionthe residue was diluted with H2O (10 mL)
  5. extractionextracted with CH2Cl2 (3×10 mL)
  6. washThe combined extracts were washed with brine (10 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (0-25% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-92d116b095f346639410d2831260afa5
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Linked notes

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