Sodium Hydroxide → 5-Bromo-2-chloro-4-methoxypyridine

HRID 2281329Notes

Reaction equation

HRID 2281329 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=1.C1C(=O)N([Br:17])C(=O)C1.[OH-].[Na+]>S(=O)(=O)(O)O.O>[Br:17][C:5]1[C:6]([O:8][CH3:9])=[CH:7][C:2]([Cl:1])=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 67184N-bromobutanimideHCID 19911282-Chloro-4-methoxypyridine

Product 1

HCID 498534155-Bromo-2-chloro-4-methoxypyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Procedure

To a solution of 2-chloro-4-methoxypyridine (10.0 g, 69.7 mmol) in 50 mL of sulfuric acid at 0° C. was added NBS. The reaction mixture was allowed to stir and warm up to room temperature for 2 hour and then heated at 60° C. for 5 hours. Then it was cooled to room temperature and neutralized with 1 N NaOH (pH ˜7), diluted with water (50 mL) and the aqueous layer was extracted with ethyl acetate (2×100 mL). The organic layers were washed with water (2×50 mL), saturated NaHCO3, brine, dried over Mg2SO4 and concentrated to provide an oil, which was chromatographed. On elution with 0-25% EtOAc/hexanes the final product was obtained.

Workup

  1. temperatureheated at 60° C. for 5 hours
  2. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
  3. washThe organic layers were washed with water (2×50 mL), saturated NaHCO3, brine
  4. dry with materialdried over Mg2SO4
  5. concentrationconcentrated
  6. customto provide an oil, which
  7. customwas chromatographed
  8. washOn elution with 0-25% EtOAc/hexanes the final product
  9. customwas obtained

Sources & evidence

ORD record
ord-b226d3042d424ede84b3631a8f4f742b
Source dataset
uspto-grants-2015_09
Patent number
US09139585B2

Reaction notes

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