Carbon Dioxide → 2,6-Dichloro-4-methoxynicotinic Acid

HRID 1753892Notes

Reaction equation

HRID 1753892 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([Cl:10])[N:3]=1.C([Li])CCC.[C:16](=[O:18])=[O:17].Cl>C1COCC1>[Cl:1][C:2]1[C:7]([C:16]([OH:18])=[O:17])=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([Cl:10])[N:3]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 33199932,6-Dichloro-4-methoxypyridineHCID 178418339Butyllithium

Product 1

HCID 593100972,6-Dichloro-4-methoxynicotinic AcidYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4.0 g (22.5 mmol) 2,6-dichloro-4-methoxy-pyridine in THF (20 ml) was added 10.0 ml (2.47 M in hexane, 24.7 mmol) n-butyllithium at −78° C. After stirring for 1 h at −78° C. excess dry ice was added and the mixture was allowed to warm to RT. Then the mixture was acidified with 6N aqueous hydrochlorid acid to pH 3-4 followed by extraction with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 4:1) provided 3.5 g (15.8 mmol, 70%) 2,6-dichloro-4-methoxy-pyridine-3-carboxylic acid.

Workup

  1. additionwas added
  2. extractionfollowed by extraction with EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by CC (hexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-b5cb3af8d0bc471aa893c4a3d9339619
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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