Ammonium Chloride → N-(3-tert-butylphenyl)-2-(2,2-dimethylpropyl)nicotinamide

HRID 2093734Notes

Reaction equation

HRID 2093734 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[CH2:3][Mg]Cl.[Cu](C#N)C#N.Br[C:14]1[N:32]=[CH:31][CH:30]=[CH:29][C:15]=1[C:16]([NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:20]=1)=[O:17].[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[C:25]([C:21]1[CH:20]=[C:19]([NH:18][C:16](=[O:17])[C:15]2[CH:29]=[CH:30][CH:31]=[N:32][C:14]=2[CH2:1][C:2]([CH3:7])([CH3:6])[CH3:3])[CH:24]=[CH:23][CH:22]=1)([CH3:28])([CH3:27])[CH3:26]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 59376154HCID 59376154, compoundHCID 178418260HCID 178418260, compoundHCID 178418809HCID 178418809, compound

Product 1

HCID 59376153N-(3-tert-butylphenyl)-2-(2,2-dimethylpropyl)nicotinamideYield 86%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2,2-Dimethylpropylmagnesium chloride (1 M-diethylether, 4.8 mL, 4.8 mmol) was added to a suspension of copper cyanide (215 mg, 2.40 mmol) in THF (6 mL) at −78° C. After stirring at the same temperature for 1 hour, 2-bromo-N-(3-tert-butylphenyl)nicotinamide (200 mg, 0.601 mmol) was added all at once as a solid. The reaction mixture was gradually warmed to room temperature and the reaction was allowed to stir overnight. Saturated ammonium chloride solution and ethyl acetate was added, and the reaction mixture was filtered through celite and rinsed with ethyl acetate. The layers were separated and the product was extracted once more with ethyl acetate. The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, the crude material was purified using silica gel column chromatography using a gradient of 20%-50% ethyl acetate in hexanes to yield N-(3-tert-butylphenyl)-2-(2,2-dimethylpropyl)nicotinamide (168 mg, 0.517 mmol, 86%). Rf=0.45 (toluene:ethyl acetate=2:1).

Workup

  1. stirringto stir overnight
  2. filtrationthe reaction mixture was filtered through celite
  3. washrinsed with ethyl acetate
  4. customThe layers were separated
  5. extractionthe product was extracted once more with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customAfter removing the solvent under reduced pressure
  9. customthe crude material was purified

Sources & evidence

ORD record
ord-c4b7484f7cf844888efb15dfa4137b17
Source dataset
uspto-grants-2013_05
Patent number
US08445515B2

Reaction notes

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