Ammonium Chloride → 6-chloro-N-methyl-4-o-tolyl-nicotinamide

HRID 379411Notes

Reaction equation

HRID 379411 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[C:12]1([CH3:20])[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Mg]Cl.[NH4+].[Cl-].[O-][Mn](=O)(=O)=O.[K+]>C1COCC1>[Cl:1][C:2]1[CH:11]=[C:10]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[CH3:20])[C:5]([C:6]([NH:8][CH3:9])=[O:7])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 516875Potassium PermanganateHCID 123642306-Chloro-N-methylnicotinamideHCID 178424304HCID 178424304, compound

Product 1

HCID 121673126-chloro-N-methyl-4-o-tolyl-nicotinamideYield 78.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1.5 g (8.8 mmol) 6-chloro-N-methyl-nicotinamide in 18 ml THF was added at 4° C. over 15 min to a solution of 21.9 ml (21.9 mmol) o-tolylmagnesium chloride 1M in THF. The reaction mixture was stirred at r.t. for 2 h cooled to 4° C. and treated dropwise over 10 min with 30.0 ml 5% aqueous NH4Cl. The aqueous phase was separated and extracted twice with THF and the organic phases were washed twice with 5% aqueous NH4Cl. The combined organic phases were dried over Na2SO4 and subsequently treated at r.t. in four portions over 10 h with 0.9 g (5.7 mmol) KMnO4. The reaction mixture was stirred for 5.5 h at r.t., filtrated and the solvent was removed. The residue was purified by chromatography over silica gel (CHCI3) to yield 1.8 g (78.9%) product as a yellow oil.

Workup

  1. temperaturecooled to 4° C.
  2. customThe aqueous phase was separated
  3. extractionextracted twice with THF
  4. washthe organic phases were washed twice with 5% aqueous NH4Cl
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. stirringThe reaction mixture was stirred for 5.5 h at r.t.
  7. filtrationfiltrated
  8. customthe solvent was removed
  9. customThe residue was purified by chromatography over silica gel (CHCI3)

Sources & evidence

ORD record
ord-d79d87b0f4f14c10999aa0bd9ed0aaa1
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Reaction notes

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