Toluene → Methyl 3-amino-6-chloropyridine-2-carboxylate

HRID 887728Notes

Reaction equation

HRID 887728 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

5

Reactant 3

HCID 1140TolueneHCID 167693Trimethylsilyldiazomethane2×HCID 533934343-Amino-6-chloropyridine-2-carboxylic acid

Product 1

HCID 58964429Methyl 3-amino-6-chloropyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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

Workup

  1. stirringthe mixture was stirred for additional 45 minutes
  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, choroform/ethyl acetate=50:1, Rf=0.30)

Sources & evidence

ORD record
ord-8a6a8d0b438c4ed88cbd54e7832eb103
Source dataset
uspto-grants-2012_08
Patent number
US08247431B2

Reaction notes

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