Methanol → Methyl 5-bromopyridine-3-carboxylate

HRID 1175596Notes

Reaction equation

HRID 1175596 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].OS(O)(=O)=O.[CH3:16]O>>[CH3:16][O:8][C:7](=[O:9])[C:6]1[CH:10]=[C:2]([Br:1])[CH:3]=[N:4][CH:5]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 887075-Bromonicotinic acid

Product 1

HCID 699336Methyl 5-bromopyridine-3-carboxylateYield 84%

Procedure

To a suspension of 5-bromonicotinic acid (20 g, 99.0 mmol) in anhydrous MeOH (100 mL), was carefully added conc. H2SO4 (12 mL) via a syringe. After the addition the reaction mixture was heated to reflux overnight, then cooled to room temperature and concentrated on rotary evaporator. Ice-water (200 mL) was added and a white solid crashed out. The solid was collected by filtration, dissolved in EtOAc (300 mL), washed with aq. NaHCO3, water and brine, dried over MgSO4, filtered and evaporated to give 18 g of 5-Bromo-nicotinic acid methyl ester as a white powder. Yield 84%. 1H NMR (400 MHz, DMSO): 3.88 (s, 3H); 0.74 (s, 3H), 8.43 (s, 1H,), 8.96 (s, 1H), 9.02 (s, 1H). MS (M+H, 217).

Workup

  1. additionAfter the addition the reaction mixture
  2. temperaturewas heated
  3. temperatureto reflux overnight
  4. concentrationconcentrated on rotary evaporator
  5. additionIce-water (200 mL) was added
  6. filtrationThe solid was collected by filtration
  7. dissolutiondissolved in EtOAc (300 mL)
  8. washwashed with aq. NaHCO3, water and brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-707364c11b654cf886e1e2b0ed03ade2
Source dataset
uspto-grants-2010_11
Patent number
US07842324B2

Reaction notes

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