Indoline → 2-[5-(2,3-Dihydro-indol-1-yl)-4'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid methyl ester

HRID 888652노트

반응식

HRID 888652 반응식
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:53][O:54][C:55](=[O:85])[CH:56]([C:61]1[CH:62]=[C:63]([C:75]2[CH:80]=[CH:79][C:78]([C:81]([F:84])([F:83])[F:82])=[CH:77][CH:76]=2)[CH:64]=[C:65](OS(C(F)(F)F)(=O)=O)[CH:66]=1)[CH2:57][CH:58]([CH3:60])[CH3:59].[NH:86]1[C:94]2[C:89](=[CH:90][CH:91]=[CH:92][CH:93]=2)[CH2:88][CH2:87]1>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:53][O:54][C:55](=[O:85])[CH:56]([C:61]1[CH:62]=[C:63]([C:75]2[CH:76]=[CH:77][C:78]([C:81]([F:83])([F:84])[F:82])=[CH:79][CH:80]=2)[CH:64]=[C:65]([N:86]2[C:94]3[C:89](=[CH:90][CH:91]=[CH:92][CH:93]=3)[CH2:88][CH2:87]2)[CH:66]=1)[CH2:57][CH:58]([CH3:59])[CH3:60]

참가 물질

7

반응물 4

HCID 10328IndolineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 59004769HCID 59004769, 화합물

생성물 1

HCID 576666612-[5-(2,3-Dihydro-indol-1-yl)-4'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid methyl ester

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 8028Tetrahydrofuran용매

반응 조건

온도
65 °C

실험 절차

A solution of Pd(OAc)2 (6 mg, 0.025 mmol) and rac-BINAP (23 mg, 0.037 mmol) in THF (2.5 mL) was stirred under nitrogen for 10 min. Cs2CO3 (95 mg, 0.29 mmol), 4-methyl-2-(5-trifluoromethanesulfonyloxy-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid methyl ester (100 mg, 0.21 mmol) and indoline (0.028 mL, 0.25 mmol) were added and the reaction mixture was stirred under nitrogen at 65° C. for 48 h. The solution was then partitioned between EtOAc (10 mL) and H2O (10 mL). The aqueous layer was extracted with EtOAc (2×10 mL). The organic layers were washed with brine, dried (MgSO4) and concentrated to yield an oil. The residue was purified by flash chromatography (0 to 10% EtOAc in petroleum ether) to give the title compound. The resulting oil was used crude in the next step.

후처리

  1. customThe solution was then partitioned between EtOAc (10 mL) and H2O (10 mL)
  2. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  3. washThe organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto yield an oil
  7. customThe residue was purified by flash chromatography (0 to 10% EtOAc in petroleum ether)

출처 및 근거

ORD 기록
ord-f1be3ef4483347ba82f106f3e0b72d61
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08247610B2

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