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

HRID 888652ノート

反応式

HRID 888652 の反応式
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]

参加物

7

反応物 4

HCID 10328IndolineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 59004769HCID 59004769、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
65 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-f1be3ef4483347ba82f106f3e0b72d61
出典データセット
uspto-grants-2012_08
特許番号
US08247610B2

反応ノート

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