Diethyl Ether → 6-Bromo-1-quinolin-4-ylmethyl-1,3-dihydro-indol-2-one

HRID 1355666Notes

Reaction equation

HRID 1355666 reaction equation
C(OC(=O)[CH:7]([C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[NH2:22])[C:8]([O:10]C(C)(C)C)=O)(C)(C)C.[N:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([CH:34]=O)=[CH:26][CH:25]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CCOCC>CC(O)=O.C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C>[Br:21][C:18]1[CH:17]=[C:16]2[C:15]([CH2:7][C:8](=[O:10])[N:22]2[CH2:34][C:27]2[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:24]=[CH:25][CH:26]=2)=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 780724-QuinolinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 700318672-(2-Amino-4-bromo-phenyl)-malonic acid di-tert-butyl ester

Product 1

HCID 185077576-Bromo-1-quinolin-4-ylmethyl-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6422Trifluoroacetic acidSolventHCID 12052TriethylsilaneSolvent

Procedure

2-(2-Amino-4-bromo-phenyl)-malonic acid di-tert-butyl ester (1.93 g, 5.0 mmol) and 4-quinolinecarboxaldehyde (890 mg, 5.50 mmol) were dissolved in 20 ml of AcOH under an atmosphere of dry N2. To this solution was added 95% NaHB(OAc)3 (1.45 g, 6.5 mmol) and the solution was stirred for 30 minutes. The reaction mixture was concentrated under vacuum and then stirred in 60 ml of a 1:1 solution of DCM/water. To this mixture was slowly added NaHCO3 until the pH˜8. The DCM layer was then washed with saturated aqueous NaHCO3 and dried over Na2SO4, filtered and concentrated under vacuum to give a golden oil which was subsequently dissolved in a solution of 20 ml of TFA and 2.5 ml of triethylsilane under an atmosphere of dry N2. The mixture was stirred overnight after which time the reaction mixture was concentrated under vacuum and then partitioned between DCM and saturated aqueous NaHCO3. The DCM layer was dried over Na2SO4, filtered and concentrated under vacuum to give a brown solid which, after trituration with Et2O, gives the tilted compound as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. stirringstirred in 60 ml of a 1:1 solution of DCM/water
  3. washThe DCM layer was then washed with saturated aqueous NaHCO3
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto give a golden oil which
  8. stirringThe mixture was stirred overnight after which time the reaction mixture
  9. concentrationwas concentrated under vacuum
  10. custompartitioned between DCM and saturated aqueous NaHCO3
  11. dry with materialThe DCM layer was dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under vacuum
  14. customto give a brown solid which

Sources & evidence

ORD record
ord-b582a2f4fc8f428fb015f877960f0346
Source dataset
uspto-grants-2003_07
Patent number
US06586447B1

Reaction notes

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