m-Toluidine → 1-Benzyl-4-(m-toluidino)piperidine-4-carbonitrile

HRID 1068486Notes

Reaction equation

HRID 1068486 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=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].C[Si]([C:27]#[N:28])(C)C.[OH-].[NH4+]>C(O)(=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:27]#[N:28])([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 7934m-ToluidineHCID 14923Ammonium HydroxideHCID 192201-Benzyl-4-piperidoneHCID 82115Trimethylsilyl cyanide

Product 1

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

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

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 a ice-water bath. After the 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. temperatureof the reaction maintained <40° C. with a ice-water bath
  2. additionAfter the addition
  3. extractionThe resultant mixture was extracted with chloroform (3 times)
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residual oil was triturated with diisopropyl ether (300 mL)
  10. stirringstirred at room temp. overnight
  11. customThe white solid precipitated
  12. filtrationwas filtered

Sources & evidence

ORD record
ord-b6faf3d60a7e4232a5630acb2402db2e
Source dataset
uspto-grants-2001_06
Patent number
US06248756B1

Reaction notes

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