Aniline → HCID 11855747, compound

HRID 900483Notes

Reaction equation

HRID 900483 reaction equation
Br[C:2]1[CH:9]=[C:8]([N:10]2[C:18]3[CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][C:14](=[O:21])[C:13]=3[CH:12]=[C:11]2[CH3:22])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CC([O-:34])(C)C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:24]1([NH:23][C:2]2[CH:9]=[C:8]([N:10]3[C:18]4[CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][C:14](=[O:21])[C:13]=4[CH:12]=[C:11]3[CH3:22])[CH:7]=[CH:6][C:3]=2[C:4]([NH2:5])=[O:34])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

7

Reactant 3

HCID 6115AnilineHCID 11855744HCID 11855744, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 11855747HCID 11855747, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

2-Bromo-4-(2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-indol-1-yl)-benzonitrile (107.2 mg, 0.3 mmol), aniline (111.8 mg, 1.2 mmol), Pd(OAc)2 (10.1 mmol, 5 mol %), DPPF (16.6 mg, 10 mol %), and NaOtBu (57.7 mg, 0.6 mmol) were placed in a Personal Chemistry Microwave Vial. The reagents were suspended in 2.5 mL of anhydrous toluene and the vessel purged with nitrogen. The reaction vessel was sealed and heated to 110° C. for 480 seconds. Upon cooling, the reaction mixture was filtered through SiO2 (eluted with 2:1 EtOAc/hexanes) and the eluent concentrated in vacuo. The residue was then dissolved in 2 mL EtOH and treated with 0.6 mL of 1 N NaOH and a catalytic amount of H2O2. After stirring this solution at 50° C. for 2 hours, the mixture of nitrile and amide was purified by column chromatography (silica, EtOAc/hexanes). The product 2-(phenylamino)-4-(2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindol-1-yl)benzamide was isolated as a yellow powder (55.6 mg, 47%). (100% clean by LC/MS, product M+H=388.1). The corresponding nitrile was also isolated (46.9 mg, 42%). (100% clean by LC/MS).

Workup

  1. customthe vessel purged with nitrogen
  2. customThe reaction vessel was sealed
  3. temperatureUpon cooling
  4. filtrationthe reaction mixture was filtered through SiO2 (eluted with 2:1 EtOAc/hexanes)
  5. concentrationthe eluent concentrated in vacuo
  6. dissolutionThe residue was then dissolved in 2 mL EtOH
  7. additiontreated with 0.6 mL of 1 N NaOH
  8. additionthe mixture of nitrile and amide
  9. customwas purified by column chromatography (silica, EtOAc/hexanes)

Sources & evidence

ORD record
ord-46f208c2c22148bb8c13ed81c944d75c
Source dataset
uspto-grants-2008_04
Patent number
US07358370B2

Reaction notes

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