Toluene → Methyl 3-aminopyridine-4-carboxylate

HRID 887698Notes

Reaction equation

HRID 887698 reaction equation
[NH2:1][C:2]1[CH:10]=[N:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:11]1(C)C=CC=CC=1.C[Si](C=[N+]=[N-])(C)C>CO>[CH3:11][O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][N:9]=[CH:10][C:2]=1[NH2:1]

Participants

5

Reactant 3

HCID 1140TolueneHCID 167693TrimethylsilyldiazomethaneHCID 4595313-Aminoisonicotinic acid

Product 1

HCID 1488824Methyl 3-aminopyridine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-Aminoisonicotinic acid (400 mg) was suspended in methanol (6 mL) and toluene (18 mL) was added. A solution of (trimethylsilyl)diazomethane (2.0 M in diethyl ether, 1.88 mL) was added slowly to the suspension. Within 5 to 10 minutes after addition, the suspension turned into a solution. After 2 hours stirring at room temperature, the reaction mixture was quenched with water and extracted 3× with ethyl acetate. The combined organic layer was washed with 2N hydrochloric acid, saturated bicarbonate solution and brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica gel 60, hexane/ethyl acetate=1:2, Rf=0.40) to afford 340 mg of the title compound of the formula

Workup

  1. additionWithin 5 to 10 minutes after addition
  2. customthe reaction mixture was quenched with water
  3. extractionextracted 3× with ethyl acetate
  4. washThe combined organic layer was washed with 2N hydrochloric acid, saturated bicarbonate solution and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuum
  7. customThe residue was purified by column chromatography (silica gel 60, hexane/ethyl acetate=1:2, Rf=0.40)

Sources & evidence

ORD record
ord-53163a636f8d405192e33f5e6dc4e498
Source dataset
uspto-grants-2012_08
Patent number
US08247431B2

Reaction notes

Loading…