Sodium Carbonate → 2'-({5-[3,5-Bis(trifluoromethyl)phenyl]-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4'-(trifluoromethyl)biphenyl-3-carbaldehyde

HRID 1994605Notes

Reaction equation

HRID 1994605 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.[CH:33]([C:35]1[CH:36]=[CH:37][C:38]([O:44][CH3:45])=[C:39](B(O)O)[CH:40]=1)=[O:34].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC=CC=1.C(O)C.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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[C:38]([O:44][CH3:45])=[CH:39][CH:40]=[C:35]([CH:33]=[O:34])[CH:36]=3)[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343675-Formyl-2-methoxyphenylboronic acidHCID 591352395-[3,5-Bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]1,3-oxazolidin-2-one

Product 1

HCID 866034382'-({5-[3,5-Bis(trifluoromethyl)phenyl]-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4'-(trifluoromethyl)biphenyl-3-carbaldehyde

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 66847609Benzene ethanol waterSolvent

Procedure

A mixture of 5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one (Example 66, 50 mg; 0.0858 mmol), 5-formyl-2-methoxyphenyl boronic acid (46 mg; 0.257 mmol), tetrakis(triphenylphosphine)palladium (0) (12 mg; 0.0103 mmol), and sodium carbonate (74 mg) in benzene/ethanol/water (2.8/0.4/1.2 mL) was heated at reflux for 60 h. The reaction was diluted with EtOAc (30 mL) and washed successively with H2O (10 mL) and brine (10 mL), dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash silica gel chromatography (0-50% EtOAc/hexanes gradient) to afford 2′-({5-[3,5-bis(trifluoromethyl)phenyl]-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4′-(trifluoromethyl)biphenyl-3-carbaldehyde as a yellow oil. LCMS=592.1 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 9.98 (s, 1H), 7.99-7.96 (m, 1H), 7.90 (s, 1H), 7.75 (s, 2H), 7.69-7.64 (m, 2 Hz), 7.53 (s, 1H), 7.41-7.38 (m, 1H), 7.17-7.14 (m, 1H), 5.37 (t, J=8.2 Hz, 1H), 4.59 (d, J=15.3 Hz, 1H), 4.37 (d, J=15.6 Hz, 1H), 3.92 (s, 3H), 3.67-3.64 (m, 1 Hz), 3.19-3.16 (m, 1H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 60 h
  3. washwashed successively with H2O (10 mL) and brine (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash silica gel chromatography (0-50% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-737a595171794e3c88217c5b724e918a
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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