Methanol → HCID 12167322, compound

HRID 379434Notes

Reaction equation

HRID 379434 reaction equation
[C:1]1([CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[Mg]Cl.[C:10]([NH:14][C:15](=[O:23])[C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[N:18][CH:17]=1)([CH3:13])([CH3:12])[CH3:11].CO.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C1COCC1>[C:10]([NH:14][C:15](=[O:23])[C:16]1[C:21]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[CH3:9])=[CH:20][C:19]([CH3:22])=[N:18][CH:17]=1)([CH3:13])([CH3:12])[CH3:11]

Participants

6

Reactant 4

HCID 887MethanolHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 10330217HCID 10330217, compoundHCID 178424304HCID 178424304, compound

Product 1

HCID 12167322HCID 12167322, compoundYield 108.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

38.9 ml (38.9 mMol) o-Tolylmagnesium chloride solution (1M in THF) were added over 15 minutes to a solution of 2.5 g (10.1 mMol) N-tert.-butyl-6-methyl-nicotinamide in 12.5 ml THF cooled to 0° C. The suspension obtained was stirred overnight at room temperature, then one more hour at 50° C. After cooling to 0° C., 2.1 ml (51.9 mMol) methanol were added over 30 minutes (exothermic!), followed after 10 minutes by 3.5 g (15.6 mMol) 2,3-dichloro-5,6-dicyano-benzoquinone. After one hour at room temperature, the reaction mixture was concentrated under reduced pressure to a still stirrable oil, heated to 50° C. and 100 ml tert.-butyl-methylether were added. The suspension was stirred 30 minutes at reflux, 1 hour at room temperature and filtered. The filtrate was evaporated and the residue was purified by flash chromatography (50 g SiO2, eluent: AcOEt/n-heptane 2:1) to yield 3.1 g (84.5%) N-tert.-butyl-6-methyl-4-o-tolyl-nicotinamide as a light brown resinous solid.

Workup

  1. customThe suspension obtained
  2. customat 50° C
  3. temperatureAfter cooling to 0° C.
  4. waitAfter one hour at room temperature
  5. concentrationthe reaction mixture was concentrated under reduced pressure to a still stirrable oil
  6. temperatureheated to 50° C.
  7. addition100 ml tert.-butyl-methylether were added
  8. stirringThe suspension was stirred 30 minutes
  9. temperatureat reflux, 1 hour at room temperature
  10. filtrationfiltered
  11. customThe filtrate was evaporated
  12. customthe residue was purified by flash chromatography (50 g SiO2, eluent: AcOEt/n-heptane 2:1)

Sources & evidence

ORD record
ord-5da68a6ab97d4ad3a04abf8a02439d3b
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Reaction notes

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