Potassium Carbonate → 1-(4-chlorophenethyl)-3-(R)-(+)-(1-cyano-1,1diphenylmethyl)piperidine

HRID 1584161Notes

Reaction equation

HRID 1584161 reaction equation
[C:1]([C:3]([C@H:16]1[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)#[N:2].[Cl:22][C:23]1[CH:31]=[CH:30][C:26]([CH2:27][CH2:28]Br)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:22][C:23]1[CH:31]=[CH:30][C:26]([CH2:27][CH2:28][N:18]2[CH2:19][CH2:20][CH2:21][C@H:16]([C:3]([C:1]#[N:2])([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=3)[CH2:17]2)=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 230291-(2-Bromoethyl)-4-chlorobenzeneHCID 228537583-(R)-(1-cyano-1,1-diphenylmethyl)-piperidine

Product 1

HCID 228537521-(4-chlorophenethyl)-3-(R)-(+)-(1-cyano-1,1diphenylmethyl)piperidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture containing 3-(R)-(+)-(1-cyano-1,1-diphenylmethyl)-piperidine (1 g--see Preparation 1), 4-chlorophenethyl bromide (0.72 g), anhydrous potassium carbonate (1.5 g) and acetonitrile (25 ml) was heated under reflux for 4 hours. The mixture was partitioned between dichloromethane (50 ml) and 10% aqueous potassium carbonate (30 ml), the layers separated, and the aqueous layer extracted with dichloromethane (3×30 ml). The combined dichloromethane extracts were dried (MgSO4) and concentrated in vacuo to give an oil which was purified by column chromatography on silica eluting with hexane containing dichloromethane (30% up to 70%) and then dichloromethane containing methanol (0% up to 5%). The product-containing fractions were combined and concentrated in vacuo to give an oil which was crystallised form acetonitrile to give the title compound as colourless rhombs, yield 0.85 g, m.p. 129-131° C., [α]D25 +20.3 (c 1.0, CH2Cl2).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 4 hours
  3. customThe mixture was partitioned between dichloromethane (50 ml) and 10% aqueous potassium carbonate (30 ml)
  4. customthe layers separated
  5. extractionthe aqueous layer extracted with dichloromethane (3×30 ml)
  6. dry with materialThe combined dichloromethane extracts were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto give an oil which
  9. customwas purified by column chromatography on silica eluting with hexane
  10. additioncontaining dichloromethane (30% up to 70%)
  11. additiondichloromethane containing methanol (0% up to 5%)
  12. concentrationconcentrated in vacuo
  13. customto give an oil which
  14. customwas crystallised form acetonitrile

Sources & evidence

ORD record
ord-c2b4dd5f6fb440479d8cc1fdb8729fd3
Source dataset
uspto-grants-1999_08
Patent number
US05932594

Reaction notes

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