Acetic Acid → 1-Benzyl-4-(m-toluidino)piperidine-4-carbonitrile

HRID 565597Notes

Reaction equation

HRID 565597 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12]C(=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].[OH-].[NH4+:24].[C:25](O)(=O)[CH3:26]>C[Si](C#N)(C)C>[CH2:1]([N:8]1[CH2:13][CH2:12][C:25]([C:26]#[N:24])([NH:19][C:18]2[CH:20]=[CH:21][CH:22]=[C:16]([CH3:15])[CH:17]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7934m-ToluidineHCID 14923Ammonium HydroxideHCID 192201-Benzyl-4-piperidone

Product 1

HCID 704161-Benzyl-4-(m-toluidino)piperidine-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 82115Trimethylsilyl cyanideSolvent

Procedure

To a solution of 1-benzyl-4-piperidone (18.9 g, 0.1 mol) and 3-methylaniline (10.7 g, 0.1 mol) in glacial acetic acid (100 mL), trimethylsilyl cyanide (6.7 mL, 0.1 mol; Journal of Organic Chemistry, vol. 55, page 4207, year 1990) was added dropwise with the temp. of the reaction maintained <40° C. with an ice-water bath. After addition was complete, the reaction mixture was stirred at room temp. for 30 min, and poured into a mixture of ice (140 g) and concentrated ammonium hydroxide (168 g). The resultant mixture was extracted with chloroform (3 times). The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residual oil was triturated with diisopropyl ether (300 mL) and stirred at room temp. overnight. The white solid precipitated was filtered to provide the title compound.

Workup

  1. additionJournal of Organic Chemistry, vol. 55, page 4207, year 1990) was added dropwise with the temp
  2. temperatureof the reaction maintained <40° C. with an ice-water bath
  3. additionAfter addition
  4. extractionThe resultant mixture was extracted with chloroform (3 times)
  5. extractionThe organic extract
  6. washwas washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residual oil was triturated with diisopropyl ether (300 mL)
  11. stirringstirred at room temp. overnight
  12. customThe white solid precipitated
  13. filtrationwas filtered

Sources & evidence

ORD record
ord-1d08c23c3b6840a8853f26c18abc9add
Source dataset
uspto-grants-2001_01
Patent number
US06172076B2

Reaction notes

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