3-Bromopyridine → 2-(Pyrrolidin-1-yl)pyridine

HRID 989661Notes

Reaction equation

HRID 989661 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C)([O-])C.[Na+].Br[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=C2C=CC(O)=C(C3C4C(=CC=CC=4)C=CC=3O)C2=CC=1>[N:15]1[CH:16]=[CH:17][CH:18]=[CH:13][C:14]=1[N:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 3

HCID 122863-BromopyridineHCID 31268PyrrolidineHCID 23676156Sodium t-butoxide

Product 1

HCID 110190202-(Pyrrolidin-1-yl)pyridineYield 221.1%

Reagents, catalysts & solvents 4

HCID 11762BinolCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of free pyrrolidine (79.3 mg; 0.22 mmol) and sodium t-butoxide (29 mg; 0.31 mmol) in dry toluene (3 mL) was added, sequentially, 3-bromopyridine (22.9 μL; 0.24 mmol), tris-(dibenzylideneacetone)dipalladium (0)(3.9 mg; cat.), and (R)-(+)-1,1′-bi-2-naphthol (5.4 mg; cat.) at room temperature under a nitrogen atmosphere. The resulting mixture was heated to 80° C., held 3 hours, then allowed to cool back to room temperature. The reaction then was diluted with ethyl acetate (40 mL), washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified via flash chromatography on silica gel (40% ethyl acetate in hexanes) to provide the N-pyridyl pyrrolidine (72.1 mg; 75%).

Workup

  1. customat room temperature
  2. temperatureto cool back to room temperature
  3. customThe reaction
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via flash chromatography on silica gel (40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5b6752b47faa48efb4419f73c89f9a8f
Source dataset
uspto-grants-2002_10
Patent number
US06458787B1

Reaction notes

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