Methanol → N-(tert-butyl)-6-chloro-4-(o-tolyl)nicotinamide

HRID 1017487Notes

Reaction equation

HRID 1017487 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]([Cl: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]([Cl:22])=[N:18][CH:17]=1)([CH3:13])([CH3:11])[CH3:12]

Participants

6

Reactant 4

HCID 887MethanolHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 11816697N-tert-butyl-6-chloronicotinamideHCID 178424304HCID 178424304, compound

Product 1

HCID 12167313N-(tert-butyl)-6-chloro-4-(o-tolyl)nicotinamideYield 90.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

92 ml (92 mMol) o-Tolylmagnesium chloride solution (1M in THF) were added over 15 minutes to a solution of 5.0 g (23 mMol) N-tert.-butyl-6-chloro-nicotinamide in 25 ml THF cooled to 0° C. The reaction mixture was stirred 18 hours at 30° C. and cooled again to 0° C. 5.6 ml (138 mMol) Methanol were added over 30 minutes, stirring was pursued for 10 minutes and 6.3 g (27 mMol) 2,3-dichloro-5,6-dicyano-1,4-benzoquinone were added. After 1 hour at room temperature, the reaction mixture was concentrated to 50 g under reduced pressure, heated to 50° C. and 100 ml tert.-butyl-methylether were added. The resulting suspension was refluxed for 30 minutes, cooled to room temperature and, after 1 hour, filtered off. The filtrate was concentrated and dried under high vacuum to yield 6.3 g (90%) of N-tert.-butyl-6-chloro-4-o-tolyl-nicotinamide as an orange foam.

Workup

  1. temperaturecooled again to 0° C
  2. stirringstirring
  3. waitwas pursued for 10 minutes
  4. waitAfter 1 hour at room temperature
  5. concentrationthe reaction mixture was concentrated to 50 g under reduced pressure
  6. temperatureheated to 50° C.
  7. addition100 ml tert.-butyl-methylether were added
  8. temperatureThe resulting suspension was refluxed for 30 minutes
  9. temperaturecooled to room temperature and, after 1 hour
  10. filtrationfiltered off
  11. concentrationThe filtrate was concentrated
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-ddbba91002d74f479d687237a97879d5
Source dataset
uspto-grants-2002_11
Patent number
US06479483B2

Reaction notes

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