Toluene → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-bromo-2'-fluoro-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 2093165Notes

Reaction equation

HRID 2093165 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([C@H: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)[C@H:14]2[CH3:31])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Br:34][C:35]1[CH:36]=[CH:37][C:38]([F:44])=[C:39](B(O)O)[CH:40]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)C>[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([C@H: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:36]=[C:35]([Br:34])[CH:40]=[CH:39][C:38]=3[F:44])[C@H:14]2[CH3:31])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 10856974(5-Bromo-2-fluorophenyl)boronic acidHCID 53363742(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 57704841(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-bromo-2'-fluoro-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one (500 mg, 0.837 mmol) was mixed with (5-bromo-2-fluorophenyl)boronic acid (211 mg, 0.963 mmol), toluene (5 mL), ethanol (278 μL) and sodium carbonate aqueous solution (2M, 0.89 mL, 1.78 mmol). The resulting mixture was stirred at 20° C. for 30 min followed by addition of tetrakis (triphenylphosphine) palladium(0) (43.5 mg, 0.0376 mmol, 4.5 mol %). The reaction mixture was heated in a 90° C. oil bath for 40 hours to complete the reaction. The resulting crude mixture was purified by flash chromatography (SiO2, Biotage 40+M cartridge). The column was eluted by an Ethyl acetate/hexanes mixture. Related fractions were pooled and concentrated in vacuo to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5′-bromo-2′-fluoro-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=645.02; found=645.94 (M+1)+.

Workup

  1. temperatureThe reaction mixture was heated in a 90° C. oil bath for 40 hours
  2. customthe reaction
  3. customThe resulting crude mixture was purified by flash chromatography (SiO2, Biotage 40+M cartridge)
  4. washThe column was eluted by an Ethyl acetate/hexanes mixture
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-60e018cfe9834523b7103055ef8ae39d
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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