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

HRID 888652Notes

Reaction equation

HRID 888652 reaction equation
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]

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-f1be3ef4483347ba82f106f3e0b72d61
Source dataset
uspto-grants-2012_08
Patent number
US08247610B2

Reaction notes

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