Reaction #51177

Reaction equation

methyl (3-formylphenyl)-5-oxopyrrolidine-3-carboxylate

2-aminopyridine

AcOH

→

methyl 5-oxo-1-{3-((2-pyridylamino)methyl)phenyl}pyrrolidine-3-carboxylate

Solvents

trimethylorthoformate

Conditions

Workup

1. 1
   ConcentrationThe reaction mixture was concentrated in vacuo
2. 2
   workup.DISSOLUTIONthe residue was re-dissolved in methanol
3. 3
   workup.ADDITIONAcOH was added
4. 4
   ConcentrationThe reaction solution was then concentrated in vacuo
5. 5
   workup.DISSOLUTIONThe residue was dissolved in EtOAc
6. 6
   Washorganic solution was washed with saturated NaHCO3 twice
7. 7
   DryingThe organic layer was dried over Na2SO4
8. 8
   Concentrationconcentrated in vacuo
9. 9
   OtherThe crude product was purified by silica gel chromatograph (10% meOH/EtOAc)
10. 10
    Otherto provide an orange oil

Procedure

A solution of methyl (3-formylphenyl)-5-oxopyrrolidine-3-carboxylate, 2-aminopyridine, and AcOH in trimethylorthoformate was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue was re-dissolved in methanol. The solution was then cooled to 0° C. AcOH was added followed by NaBH3CN solid in portions. The reaction was allowed to stirred at room temperature for 8 hours. The reaction solution was then concentrated in vacuo. The residue was dissolved in EtOAc and organic solution was washed with saturated NaHCO3 twice. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel chromatograph (10% meOH/EtOAc) to provide an orange oil.

Source