Bicarbonate Ion → 2-Chloro-4,6-dimethylpyridine

HRID 880468

Reaction equation

HRID 880468 reaction equation
N[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.[Cl-:10].[Na+].N([O-])=O.[Na+].C(=O)(O)[O-]>Cl.O>[Cl:10][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1

Participants

7

Reactant 4

HCID 769Bicarbonate IonHCID 5234Sodium Chloride2×HCID 215072-Amino-4,6-dimethylpyridineHCID 23668193Sodium Nitrite

Product 1

HCID 125083782-Chloro-4,6-dimethylpyridineYield 38.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Procedure

A mixture of 2-amino-4,6-dimethylpyridine (90 g, 0.736 mol) and sodium chloride (216 g, 3.69 mol) in concentrated hydrochloric acid (720 mL) was cooled to between −15 and −20° C. A solution of sodium nitrite (71.2 g, 1.03 mol) in water (135 mL) was added over 30 min. More sodium chloride (216 g, 3.69 mol) was added and the reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. The reaction mixture was basified with solid bicarbonate (700 g) and extracted with dichloromethane (1 L), filtered and the two phases separated. The organic layer was concentrated in vacuo and the crude purified by flash column chromatography over silica gel (100-200 mesh) with 20% dichloromethane in petroleum ether as eluent to afford 2-chloro-4,6-dimethylpyridine (40 g, 38%) as a solid.

Workup

  1. temperaturewas cooled to between −15 and −20° C
  2. extractionextracted with dichloromethane (1 L)
  3. filtrationfiltered
  4. customthe two phases separated
  5. concentrationThe organic layer was concentrated in vacuo
  6. customthe crude purified by flash column chromatography over silica gel (100-200 mesh) with 20% dichloromethane in petroleum ether as eluent

Sources & evidence

ORD record
ord-954cae20cb8e47b4afe63beaa3c037ca
Source dataset
uspto-grants-2015_03
Patent number
US08993574B2

Linked notes

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