Hydrochloric Acid → 5-Bromo-3-chloro-2-methylpyridine

HRID 539289Notes

Reaction equation

HRID 539289 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([Cl:19])[C:5]([CH:8](C(OCC)=O)C(OCC)=O)=[N:6][CH:7]=1.Cl>>[Br:1][C:2]1[CH:3]=[C:4]([Cl:19])[C:5]([CH3:8])=[N:6][CH:7]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 67979448Diethyl 2-(5-bromo-3-chloropyridin-2-yl)malonate2×

Product 1

HCID 299278745-Bromo-3-chloro-2-methylpyridineYield 51%

Procedure

A solution of impure diethyl 2-(5-bromo-3-chloropyridin-2-yl)malonate (Intermediate 42, 0.41 g, 1.2 mmol) and cone. aq. HCl (3 mL) was heated at reflux for 3 h. The volatiles were removed in vacuo, and the residue was co-evaporated with acetonitrile. The residual solid (mono-decarboxylated acid) was dissolved in dioxane (4.5 mL) and heated at reflux overnight. The volatiles were removed in vacuo. The residue was purified by flash chromatography (4 g SiO2, heptane/EtOAc gradient) affording the title compound (0.12 g, 51% yield): 1H NMR (500 MHz, CDCl3) δ ppm 2.60 (s, 3 H), 7.82 (d, 1 H), 8.46 (d, 1 H); MS (CI) m/z 206 [M+H]+.

Workup

  1. temperatureat reflux for 3 h
  2. customThe volatiles were removed in vacuo
  3. dissolutionThe residual solid (mono-decarboxylated acid) was dissolved in dioxane (4.5 mL)
  4. temperatureheated
  5. temperatureat reflux overnight
  6. customThe volatiles were removed in vacuo
  7. customThe residue was purified by flash chromatography (4 g SiO2, heptane/EtOAc gradient)

Sources & evidence

ORD record
ord-00a943d4e2d84b078376867a426110bf
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

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