Toluene → Methyl 3-amino-6-chloropicolinate

Reaction equation

[NH2:1][C:2]1[C:3]([C:9]([OH:11])=[O:10])=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.[C:12]1(C)C=CC=CC=1.C[Si](C=[N+]=[N-])(C)C>CO>[CH3:12][O:10][C:9]([C:3]1[C:2]([NH2:1])=[CH:7][CH:6]=[C:5]([Cl:8])[N:4]=1)=[O:11]

Participants

Procedure

3-Amino-6-chloro-pyridine-2-carboxylic acid (636 mg) was suspended in methanol (8 mL) and toluene (22 mL) was added. A solution of (trimethylsilyl)diazomethane (2.0 M in hexane, 2.4 mL) was added slowly to the reaction mixture. After 1 hour stirring at room temperature, another portion of (trimethylsilyl)diazomethane (550 μl) was added and the mixture was stirred for additional 45 minutes. 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, choroform/ethyl acetate=50:1, Rf=0.30) to afford 365 mg of the title compound of the formula