Toluene → HCID 66657313, compound

HRID 660106Notes

Reaction equation

HRID 660106 reaction equation
C1(C)C=CC=CC=1.[C:8]([O:12][C:13]([N:15]1[CH2:19][CH2:18][C@H:17]([NH2:20])[CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].Br[C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[C:25]#[N:26].C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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.ClCCl.O>[C:8]([O:12][C:13]([N:15]1[CH2:19][CH2:18][C@H:17]([NH:20][C:22]2[CH:29]=[CH:28][CH:27]=[C:24]([C:25]#[N:26])[CH:23]=2)[CH2:16]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

9

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 233813-BromobenzonitrileHCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylate

Product 1

HCID 66657313HCID 66657313, compoundYield 54.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a toluene solution (7 ml) containing 2.82 g of 3(S)-aminopyrrolidine-1-carboxylic acid tert-butyl ester (15 mmol) and 1.82 g of 3-bromobenzonitrile (10 mmol) were added 68.5 mg of BINAP (0.11 mmol), 22.5 mg of palladium acetate (0.1 mmol) and 3.91 g of cesium carbonate (12 mmol). The mixture was heated under reflux under a nitrogen atmosphere for 8 hours. After cooling to room temperature, water was added to the reaction solution, and extraction with dichloromethane was performed. After drying over sodium sulfate and concentration under reduced pressure, the residue was then purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1). The purified product was concentrated to dryness under reduced pressure to thereby obtain 1.56 g of light yellow powdery 3(S)-(3-cyanophenylamino)pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux under a nitrogen atmosphere for 8 hours
  3. dry with materialAfter drying over sodium sulfate and concentration under reduced pressure
  4. customthe residue was then purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1)
  5. concentrationThe purified product was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-a201e920945c40818541e4e908fa9b43
Source dataset
uspto-grants-2011_12
Patent number
US08084442B2

Reaction notes

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