Bromine → Methyl 2-amino-5-bromopyridine-4-carboxylate

HRID 1984572Notes

Reaction equation

HRID 1984572 reaction equation
[Br:1]Br.[CH3:3][O:4][C:5](=[O:13])[C:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH2:12])[CH:7]=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)(Cl)Cl>[CH3:3][O:4][C:5](=[O:13])[C:6]1[C:11]([Br:1])=[CH:10][N:9]=[C:8]([NH2:12])[CH:7]=1

Participants

5

Reactant 3

HCID 24408BromineHCID 24477Sodium ThiosulfateHCID 236984Methyl 2-aminopyridine-4-carboxylate

Product 1

HCID 25307230Methyl 2-amino-5-bromopyridine-4-carboxylateYield 23%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Bromine (1.78 ml, 34.8 mmol) was added dropwise over an hour to a stirred solution of 2-amino-isonicotinic acid methyl ester (5.13 g, 33.75 mmol) in chloroform (350 ml) at room temperature and the orange solution stirred at room temperature overnight. A 2N solution of sodium thiosulfate (300 ml) was added to the reaction and stirred for ten minutes. The two layers were separated and the aqueous extracted with chloroform (100 ml). The combined organics were dried (MgSO4) and concentrated under reduced pressure. The desired isomer was purified by flash column chromatography using ethyl acetate 2/3 hexane as eluent to afford 2-amino-5-bromo-isonicotinic acid methyl ester as a yellow solid (1.79 g, 23%). 1H NMR (CDCl3): 8.21 (1H, s, py); 6.79 (1H, s, py); 4.53 (2H, br s, NH2); 3.88 (3H, S, CO2CH3).

Workup

  1. stirringstirred for ten minutes
  2. customThe two layers were separated
  3. extractionthe aqueous extracted with chloroform (100 ml)
  4. dry with materialThe combined organics were dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe desired isomer was purified by flash column chromatography

Sources & evidence

ORD record
ord-ad476ab9d6e74bbb9114d61db4bd47f7
Source dataset
uspto-grants-2009_06
Patent number
US07544702B2

Reaction notes

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