Sulfuric Acid → 6-Tert-butyl-2-(3,3-dimethylbut-1-ynyl)nicotinaldehyde

HRID 921044Notes

Reaction equation

HRID 921044 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[C:11]([C:15]1[CH:22]=[CH:21][C:18]([C:19]#N)=[C:17]([C:23]#[C:24][C:25]([CH3:28])([CH3:27])[CH3:26])[N:16]=1)([CH3:14])([CH3:13])[CH3:12].S(=O)(=O)(O)[OH:30].[OH-].[Na+]>C1(C)C=CC=CC=1.ClCCl.O.C1COCC1>[C:11]([C:15]1[N:16]=[C:17]([C:23]#[C:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:18]([CH:19]=[O:30])=[CH:21][CH:22]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

9

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 21225700DiisobutylaluminumhydrideHCID 679961326-tert-Butyl-2-(3,3-dimethylbut-1-ynyl)nicotinonitrile

Product 1

HCID 866802546-Tert-butyl-2-(3,3-dimethylbut-1-ynyl)nicotinaldehyde

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

310 ml (315 mmol) of diisobutylaluminium hydride, 1M in toluene, are added dropwise to a solution, cooled to −78° C., of 72.1 g (300 mmol) of 6-tert-butyl-2-(3,3-dimethylbut-1-ynyl)nicotinonitrile, S62, in 1500 ml of dichloromethane at such a rate that the temperature does not exceed −65° C. When the addition is complete, the reaction mixture is stirred at −78° C. for a further 2 h, then allowed to warm slowly to room temperature and stirred for a further 12 h. After re-cooling to −10° C., 300 ml of THF and then, with vigorous stirring, 400 ml of 2 N sulfuric acid (exothermic!) are added, and the mixture is stirred at room temperature for a further 12 h. After re-cooling to −10° C., a solution of 70 g of NaOH in 300 ml of water is added, the aqueous phase is separated off, the organic phase is washed three times with 1000 ml of water each time, once with 500 ml of saturated sodium chloride solution, dried over magnesium sulfate, and the solvent is removed in vacuo.

Workup

  1. customdoes not exceed −65° C
  2. additionWhen the addition
  3. temperatureto warm slowly to room temperature
  4. stirringstirred for a further 12 h
  5. temperatureAfter re-cooling to −10° C.
  6. stirringthe mixture is stirred at room temperature for a further 12 h
  7. temperatureAfter re-cooling to −10° C.
  8. customthe aqueous phase is separated off
  9. washthe organic phase is washed three times with 1000 ml of water each time
  10. dry with materialonce with 500 ml of saturated sodium chloride solution, dried over magnesium sulfate
  11. customthe solvent is removed in vacuo

Sources & evidence

ORD record
ord-814602ba4ae84b7aafabde5aff5e0484
Source dataset
uspto-grants-2016_03
Patent number
US09273080B2

Reaction notes

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