Ammonium Hydroxide → 4,6-Dichloronicotinamide

HRID 1255713Notes

Reaction equation

HRID 1255713 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[C:13]([C:14](O)=[O:15])=[CH:12][N:11]=[C:10]([Cl:17])[CH:9]=1.[NH4+:18].[OH-]>CN(C)C=O.O>[Cl:7][C:8]1[C:13]([C:14]([NH2:18])=[O:15])=[CH:12][N:11]=[C:10]([Cl:17])[CH:9]=1

Participants

6

Reactant 3

HCID 14923Ammonium Hydroxide2×HCID 65578Oxalyl chlorideHCID 8171584,6-Dichloronicotinic acid

Product 1

HCID 6000444,6-DichloronicotinamideYield 95.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Oxalyl chloride (7.70 mL, 88.3 mmol) was added over 1 hour to a suspension of 4,6-dichloronicotinic acid (8.47 g, 44.1 mmol) in dimethylformamide (200 mL) at room temperature. The reaction mixture was stirred for an additional 3 hours at room temperature then concentrated in vacuo. The residue was dissolved in CH2Cl2 (200 mL) followed by the dropwise addition of NH4OH (8.3 mL, 130 mmol) over 30 minutes [Note: reaction is exothermic upon addition of NH4OH and care was taken to control the rate of addition so that the reaction temperature did not exceed 25° C.]. The reaction mixture was stirred for an additional 1 hour at room temperature then diluted with water (600 mL) and extracted with EtOAc (4×600 mL). The organic extracts were combined, dried over Na2SO4, filtered and concentrated to give the title compound as a light brown solid (8.05 g, 95% yield). This material was carried forward without further purification.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2 (200 mL)
  3. customreaction
  4. additionthe rate of addition so that the reaction temperature
  5. customdid not exceed 25° C.
  6. stirringThe reaction mixture was stirred for an additional 1 hour at room temperature
  7. extractionextracted with EtOAc (4×600 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-e0ab08f637f547a798a5ce80e0634161
Source dataset
uspto-grants-2013_06
Patent number
US08461135B2

Reaction notes

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