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 1994643Notes

Reaction equation

HRID 1994643 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-6f9763a480684ed1afc64da68816d3fc
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

Loading…