3-Pyridinylboronic acid → Methyl 2-amino-3-nitro-5-(3-pyridinyl)benzoate

HRID 447026Notes

Reaction equation

HRID 447026 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8](Br)[CH:7]=[C:6]([N+:11]([O-:13])=[O:12])[C:5]=1[NH2:14].[N:16]1[CH:21]=[CH:20][CH:19]=[C:18](B(O)O)[CH:17]=1>COCCOC.C(=O)([O-])O.[Na+]>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([C:18]2[CH:17]=[N:16][CH:21]=[CH:20][CH:19]=2)[CH:7]=[C:6]([N+:11]([O-:13])=[O:12])[C:5]=1[NH2:14]

Participants

5

Reactant 2

HCID 27343783-Pyridinylboronic acidHCID 17984898Methyl 2-amino-5-bromo-3-nitrobenzoate

Product 1

HCID 59337640Methyl 2-amino-3-nitro-5-(3-pyridinyl)benzoate

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 516892Sodium BicarbonateSolvent2×

Procedure

A stirred solution of 2-Amino-5-bromo-3-nitro-benzoic acid methyl ester (2 g, 7.27 mmol) in 1,2-dimethoxyethane (53 ml) was purged with nitrogen for 15 min and treated with aqueous sodium hydrogen carbonate solution (1M, 14.5 ml) followed by pyridine 3-boronic acid (1.33 g, 10.9 mmol) and 1,1-bis-(diphenylphosphino)ferrocene palladium (II) chloride complex (0.6 g, 0.733 mmol). The resultant mixture was boiled under reflux in a nitrogen atmosphere for 18 h. After cooling to ambient temperature, the dark mixture was diluted with saturated aqueous sodium hydrogen carbonate solution (300 ml) and extracted with ethyl acetate (3×250 ml). This was washed with brine (200 ml), dried (MgSO4) and the solvent removed in vacuo to give a residue which was purified by flash chromatography (silica) eluting with 30% to 100% ethyl acetate in 40-60 petroleum ether. The 2-Amino-3-nitro-5-pyridin-3-yl-benzoic acid methyl ester was obtained as a yellow solid (1.1 g, 56%).

Workup

  1. temperatureunder reflux in a nitrogen atmosphere for 18 h
  2. extractionextracted with ethyl acetate (3×250 ml)
  3. washThis was washed with brine (200 ml)
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customto give a residue which
  7. customwas purified by flash chromatography (silica)
  8. washeluting with 30% to 100% ethyl acetate in 40-60 petroleum ether

Sources & evidence

ORD record
ord-9085932c50ef408eaed36191d6922f99
Source dataset
uspto-grants-2013_07
Patent number
US08481544B2

Reaction notes

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