Acetic Acid → N-benzyl-6-chloro-4-o-tolyl-nicotinamide

HRID 379421Notes

Reaction equation

HRID 379421 reaction equation
[CH2:1]([NH:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[N:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:18]1([CH3:26])[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[Mg]Cl.C(O)(=O)C>C1COCC1.O.O.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Mn+3]>[CH2:1]([NH:8][C:9](=[O:17])[C:10]1[C:15]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[CH3:26])=[CH:14][C:13]([Cl:16])=[N:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 857488N-Benzyl-6-chloro-nicotinamideHCID 178424304HCID 178424304, compound

Product 1

HCID 12167314N-benzyl-6-chloro-4-o-tolyl-nicotinamideYield 89.1%

Reagents, catalysts & solvents 2

HCID 12416832Manganese triacetate dihydrateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 0.5 g (2.0 mMol) N-benzyl-6-chloro-nicotinamide in 5.0 ml THF was added over 25 minutes to 10.1 ml (10.1 mMol) of o-tolylmagnesium chloride solution (1M in THF) cooled to 0° C. After 2.5 hours stirring at room temperature, the reaction mixture was cooled again to 0° C. and 4.0 ml acetic acid were added over 15 minutes followed by 1.1 g (4.1 mMol) manganese triacetate dihydrate. After stirring for 1 hour at room temperature, the reaction mixture was filtered and the filtrate was poured onto 20 ml deionized water. Sodium bicarbonate was added portionwise to bring the pH to 7 and the phases were separated. The aqueous layer was extracted with dichloromethane. The combined organic extracts were washed with water, dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (eluent ethyl acetate/n-hexane 2:1) to yield 0.6 g (88%) N-benzyl-6-chloro-4-o-tolyl-nicotinamide as an orange resin.

Workup

  1. temperaturethe reaction mixture was cooled again to 0° C.
  2. stirringAfter stirring for 1 hour at room temperature
  3. filtrationthe reaction mixture was filtered
  4. additionthe filtrate was poured onto 20 ml
  5. additionSodium bicarbonate was added portionwise
  6. customthe phases were separated
  7. extractionThe aqueous layer was extracted with dichloromethane
  8. washThe combined organic extracts were washed with water
  9. dry with materialdried (Na2SO4)
  10. customevaporated
  11. customThe residue was purified by flash chromatography (eluent ethyl acetate/n-hexane 2:1)

Sources & evidence

ORD record
ord-9c1004844e1743f5ab97ad94b3f4675d
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Reaction notes

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