Hydrochloric Acid → 6-Bromo-3-chloro-2-methoxypyridine

HRID 70523Notes

Reaction equation

HRID 70523 reaction equation
N([O-])=O.[Na+].[Br:5][C:6]1[N:11]=[C:10]([O:12][CH3:13])[C:9](N)=[CH:8][CH:7]=1.[ClH:15]>O.[Cu](Cl)Cl>[Br:5][C:6]1[N:11]=[C:10]([O:12][CH3:13])[C:9]([Cl:15])=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 105361376-Bromo-2-methoxypyridin-3-amineHCID 23668193Sodium Nitrite

Product 1

HCID 584523026-Bromo-3-chloro-2-methoxypyridineYield 85%

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 962WaterSolvent2×

Procedure

A solution of sodium nitrite (7.04 g) in water (10 mL) was added dropwise to a suspension of 6-bromo-2-methoxypyridin-3-amine (10.4 g) in concentrated hydrochloric acid (35 mL) under ice-cooling. After stirring for 10 minutes, the reaction system was added dropwise to a suspension of copper chloride (12.7 g) in concentrated hydrochloric acid (15 mL) under ice-cooling, and the mixture was stirred at 65° C. for one hour and 15 minutes. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→7:3) to give the title compound as a yellow powder (9.69 g, 85%).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred at 65° C. for one hour and 15 minutes
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationAfter filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→7:3)

Sources & evidence

ORD record
ord-0b4c2e290aea47d6954e1ee05dd0c359
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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