Iodine → Ethyl 5-amino-6-iodo-4-methylpyridine-2-carboxylate

HRID 1512981Notes

Reaction equation

HRID 1512981 reaction equation
[NH2:1][C:2]1[C:3]([CH3:13])=[CH:4][C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:6][CH:7]=1.II.[I:16]([O-])(=O)(=O)=O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>CN(C)C=O>[NH2:1][C:2]1[C:3]([CH3:13])=[CH:4][C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:6][C:7]=1[I:16]

Participants

6

Reactant 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 23667635Sodium periodateHCID 53404692HCID 53404692, compound

Product 1

HCID 86641273Ethyl 5-amino-6-iodo-4-methylpyridine-2-carboxylateYield 132.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of ethyl 5-amino-4-methylpyridine-2-carboxylate (2.58 g), iodine (2.91 g) and sodium periodate (1.22 g) in N,N-dimethylformamide (20 mL) was stirred at 60° C. for 6 days. The reaction mixture was cooled to room temperature. To the reaction mixture was added 1 mol/L aqueous sodium thiosulfate solution, and the resulting mixture was extracted with ethyl acetate twice. The extracts were washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=2/1−1/1) to give ethyl 5-amino-6-iodo-4-methylpyridine-2-carboxylate (2.31 g). To sodium hexamethyldisilazide (1.03 mol/L tetrahydrofuran solution, 10.5 mL) was added a solution of ethyl 5-amino-6-iodo-4-methylpyridine-2-carboxylate (1.51 g) in tetrahydrofuran (9 mL) in a dropwise manner at −10° C., and the mixture was stirred at the same temperature for 10 minutes. To the mixture was added a solution of di(tert-butyl)dicarbonate (1.18 g) in tetrahydrofuran (4 mL) in a dropwise manner, and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1−2/1) to give the title compound (1.11 g).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe resulting mixture was extracted with ethyl acetate twice
  3. washThe extracts were washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=2/1−1/1)

Sources & evidence

ORD record
ord-8067105466984c4e881dde0330f1fab6
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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