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

HRID 1366820Notes

Reaction equation

HRID 1366820 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 (1 H, s, py); 6.79 (1 H, s, py); 4.53 (2 H, br s, NH2); 3.88 (3 H, 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-13fe5dd897af41a1bf08a681d7075515
Source dataset
uspto-grants-2011_02
Patent number
US07893077B2

Reaction notes

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