(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one → 2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)benzonitrile

HRID 505256Notes

Reaction equation

HRID 505256 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.[C:34]([Cu])#[N:35]>CN(C=O)C.CCOC(C)=O>[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:34]#[N:35])[C@H:14]2[CH3:31])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 2

HCID 53363742(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-oneHCID 178418546HCID 178418546, compound

Product 1

HCID 866287512-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (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) in DMF (7.5 mL) was added CuCN (150 mg, 1.67 mmol). The reaction was heated to 100° C. and stirred at that temperature for 14 hours. The reaction was then cooled to room temperature, diluted with EtOAc (200 mL), and washed with 100 mL of 2.5 M aqueous ammonia. The organic layer was washed with brine (75 mL) and then filtered through a plug of silica gel. The filtrate was concentrated, and the residue was purified by flash chromatography on silica gel (5 to 50% EtOAc/hexanes) to afford 2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)benzonitrile. Rf=0.29 (25% EtOAc/hexanes). LCMS=497.0 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.91 (s, 1H), 7.88 (s, 1H), 7.86 (d, J=8.2 Hz, 1H), 7.79 (s, 2H), 7.74 (d, J=8.2 Hz, 1H), 5.78 (d, J=7.8 Hz, 1H), 4.93 (d, J=16.1 Hz, 1H), 4.53 (d, J=15.8 Hz, 1H), 4.23 (m, 1H), 0.86 (d, J=6.7 Hz, 3H).

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. washwashed with 100 mL of 2.5 M aqueous ammonia
  3. washThe organic layer was washed with brine (75 mL)
  4. filtrationfiltered through a plug of silica gel
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by flash chromatography on silica gel (5 to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f47534db91a74cb4942104e08b3b0c84
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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