Ethanol → (4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-5-[5'-isopropyl-2'-(trifluoromethoxy)-4-(trifluoromethyl)biphenyl-2-yl]-4-methyl-1,3-oxazolidin-2-one

HRID 1028676Notes

Reaction equation

HRID 1028676 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]1[C@H:11]([CH3:12])[C@@H:10]([C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2I)[O:9][C:8]1=[O:24].C(O)C.[CH:37]([C:40]1[CH:41]=[CH:42][C:43]([O:49][C:50]([F:53])([F:52])[F:51])=[C:44](B(O)O)[CH:45]=1)([CH3:39])[CH3:38].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC=CC=1.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:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]1[C@H:11]([CH3:12])[C@@H:10]([C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2[C:42]2[CH:41]=[C:40]([CH:37]([CH3:39])[CH3:38])[CH:45]=[CH:44][C:43]=2[O:49][C:50]([F:51])([F:53])[F:52])[O:9][C:8]1=[O:24]

Participants

9

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 59135170(4R,5R)-3-[3,5-Bis(trifluoromethyl)benzyl]-5-[2-iodo-5-(trifluoromethyl)phenyl)-4-methyl-1,3-oxazolidin-2-oneHCID 667170385-Isopropyl-2-(trifluoromethoxy)phenyl boronic acid

Product 1

HCID 11563769(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-5-[5'-isopropyl-2'-(trifluoromethoxy)-4-(trifluoromethyl)biphenyl-2-yl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 80 mg of (4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-5-[2-iodo-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one in 2 mL of benzene, 1 mL of water, and 0.5 mL ethanol was added 100 mg of 5-isopropyl-2-(trifluoromethoxy)phenyl boronic acid, 0.15 mL of 2M aqueous sodium carbonate, and 21 mg of Pd(PPh3)4. A reflux condenser was attached, and the mixture was heated to 100° C. The mixture was stirred at 100° C. for 24 hours, and then was diluted with 10 mL of EtOAc and 10 mL of water. The phases were separated and the aqueous phase was extracted with 10 mL of EtOAc. The combined organic phases were washed with 10 mL of brine, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography on a Biotage Horizon, 25M column, eluting with 1 CV of 2% EtOAc in hexanes, followed by a linear gradient of EtOAc in hexanes from 2 to 100% over 10 CV. The product was repurified using the same conditions to provide the title compound. Mass spectrum (ESI) 674.4 (M+1).

Workup

  1. customA reflux condenser was attached
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with 10 mL of EtOAc
  4. washThe combined organic phases were washed with 10 mL of brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on a Biotage Horizon, 25M column
  8. washeluting with 1 CV of 2% EtOAc in hexanes
  9. customThe product was repurified

Sources & evidence

ORD record
ord-ec12f2bb354b4de3bb8604d32d8ff23e
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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