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 1028676노트

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HRID 1028676 반응식
[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]

참가 물질

9

반응물 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

생성물 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

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 241Benzene용매HCID 962Water용매2회HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-ec12f2bb354b4de3bb8604d32d8ff23e
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735435B2

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