Ammonia → 2,6-Difluoropyridine-3-carboxamide

HRID 50834Notes

Reaction equation

HRID 50834 reaction equation
[F:1][C:2]1[N:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].O=S(Cl)Cl.[NH3:16]>ClCCCl.CN(C=O)C>[F:1][C:2]1[N:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH2:16])=[O:5]

Participants

6

Reactant 3

HCID 222AmmoniaHCID 24386Thionyl ChlorideHCID 105830702,6-Difluoropyridine-3-carboxylic acid

Product 1

HCID 105830482,6-Difluoropyridine-3-carboxamideYield 77,136.102%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution 2,6-difluoronicotinic acid (7.4 g, 0.046 mmol) and SOCl2 (20 mL) in 1,2-dichloroethane (60 mL) containing DMF (1 drop) is heated under reflux for 4 h, then concentrated to dryness under reduced pressure. The residue is dissolved in Et2O (100 mL), cooled to 0° C., and treated dropwise with concentrated ammonia (10.0 mL, 0.17 mmol). After 10 min the solution is washed with aqueous NaHCO3 and worked up to give 2,6-difluoronicotinamide (5.61 g, 76%). 1H NMR (CDCl3) a 8.70 (1H, dd, J=9.6, 8.3 Hz), 7.00 (1H, ddd, J=8.3, 2.9, 1.1 Hz), 6.71, 6.55 (1H, 1H, 2 brs)

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 4 h
  3. concentrationconcentrated to dryness under reduced pressure
  4. dissolutionThe residue is dissolved in Et2O (100 mL)
  5. washAfter 10 min the solution is washed with aqueous NaHCO3

Sources & evidence

ORD record
ord-24264ffa5dd743e5b4dd3cbc634fc8a8
Source dataset
uspto-grants-2004_03
Patent number
US06713484B2

Reaction notes

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