Iodine → Methyl 2-(6-amino-5-iodopyridin-3-yl)-2-methylpropanoate

HRID 609874Notes

Reaction equation

HRID 609874 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([CH3:14])([CH3:13])[C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.[I:15]I>CO.FC(F)(F)C([O-])=O.[Ag+]>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([CH3:14])([CH3:13])[C:9]([O:11][CH3:12])=[O:10])=[CH:4][C:3]=1[I:15]

Participants

5

Reactant 2

HCID 807IodineHCID 21998700Methyl 2-(6-aminopyridin-3-yl)-2-methylpropanoate

Product 1

HCID 15887215Methyl 2-(6-amino-5-iodopyridin-3-yl)-2-methylpropanoateYield 62.5%

Reagents, catalysts & solvents 2

HCID 76299Silver trifluoroacetateCatalystHCID 887MethanolSolvent2×

Procedure

A solution of methyl 2-(6-aminopyridin-3-yl)-2-methylpropanoate (10.0 g, 51.5 mmol) in MeOH (50 mL) was added over approximately 0.5 h via pressure equalizing addition funnel to a vigorously stirred suspension of iodine (17.0 g, 67.0 mmol) and silver trifluoroacetate (14.8 g, 67.0 mmol) in MeOH (200 mL) at room temperature. After 3 h, the reaction was quenched sequentially with 1M Na2S2O3 followed by saturated aqueous NaHCO3. The resulting mixture was filtered through celite® washing copiously with ethyl acetate, the filtrate concentrated in vacuo and the residue partitioned between ethyl acetate and water. The organic phase was separated and the aqueous phase was re-extracted with ethyl acetate (×3). The combined organic extract was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (gradient elution; 35-40% ethyl acetate/hexanes as eluent) to give the title compound as an off-white solid (10.3 g, 62%).

Workup

  1. additionaddition funnel
  2. customthe reaction was quenched sequentially with 1M Na2S2O3
  3. filtrationThe resulting mixture was filtered through celite®
  4. washwashing copiously with ethyl acetate
  5. concentrationthe filtrate concentrated in vacuo
  6. customthe residue partitioned between ethyl acetate and water
  7. customThe organic phase was separated
  8. extractionthe aqueous phase was re-extracted with ethyl acetate (×3)
  9. extractionThe combined organic extract
  10. washwas washed with brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash chromatography on silica gel (gradient elution; 35-40% ethyl acetate/hexanes as eluent)

Sources & evidence

ORD record
ord-2a678146a5fd47358b4ea68842181836
Source dataset
uspto-grants-1999_12
Patent number
US05998432

Reaction notes

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