2-Chloronicotinic acid → 2-(2-Methylpropoxy)pyridine-3-carboxylic acid

HRID 354161Notes

Reaction equation

HRID 354161 reaction equation
[Na].Cl[C:3]1[N:11]=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=[O:6]>C(O)C(C)C>[CH2:5]([O:6][C:3]1[N:11]=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=[O:6])[CH:4]([CH3:8])[CH3:3]

Participants

4

Reactant 2

HCID 762582-Chloronicotinic acidHCID 5360545Sodium

Product 1

HCID 235115682-(2-Methylpropoxy)pyridine-3-carboxylic acidYield 168.1%

Reagents, catalysts & solvents 1

HCID 6560IsobutanolSolvent2×

Conditions

Temperature
80 °C

Procedure

Sodium metal (3 g, 0.127 mol) was added in small amounts to isobutanol (100 mL)—some warming (80° C.) was needed to facilitate dissolution. 2-Chloronicotinic acid (10 g, 0.064 mol) was added and the solution refluxed for 1 h. A thick mixture resulted and a further 100 mL isobutanol was added and the mixture refluxed for 3 h. The mixture was cooled and quenched with 2N hydrochloric acid. The product was extracted into ethyl acetate and the organics washed with dilute hydrochloric acid (pH 3), dried (MgSO4) and concentrated to give a brown solid. Purification by flash column chromatography (ethyl acetate as eluant) gave 10.5 g of product as a yellow solid.

Workup

  1. dissolutiondissolution
  2. temperaturethe solution refluxed for 1 h
  3. customA thick mixture resulted
  4. temperaturethe mixture refluxed for 3 h
  5. temperatureThe mixture was cooled
  6. customquenched with 2N hydrochloric acid
  7. extractionThe product was extracted into ethyl acetate
  8. washthe organics washed with dilute hydrochloric acid (pH 3)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customto give a brown solid
  12. customPurification by flash column chromatography (ethyl acetate as eluant)

Sources & evidence

ORD record
ord-017b6a9dc9654a8cb6db2f40c208bcf4
Source dataset
uspto-grants-2004_06
Patent number
US06756373B1

Reaction notes

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