Reaction #49665

Reaction equation

3-(R)-(+)-(1-cyano-1,1-diphenylmethyl)piperidine

4-hydroxymethylphenethyl bromide

potassium carbonate

→

title compound

3-(R)-(+)-(1-cyano-1,1-diphenylmethyl)-1-(4-hydroxymethylphenethyl)piperidine

Solvents

acetonitrile

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureunder reflux for 5 hours
3. 3
   OtherThe mixture was partitioned between dichloromethane (30 ml) and 10% aqueous potassium carbonate (20 ml)
4. 4
   Otherthe layers separated
5. 5
   Extractionthe aqueous layer extracted with dichloromethane (2×20 ml)
6. 6
   DryingThe combined dichloromethane extracts were dried (MgSO4)
7. 7
   Concentrationconcentrated in vacuo
8. 8
   Otherto give an oil which
9. 9
   Otherwas purified by column chromatography on silica eluting with hexane
10. 10
    workup.ADDITIONcontaining dichloromethane (30% up to 70%)
11. 11
    workup.ADDITIONdichloromethane containing methanol (0% up to 5%)
12. 12
    Concentrationconcentrated in vacuo
13. 13
    Otherto give an oil which
14. 14
    Otherwas crystallised from acetonitrile

Procedure

A mixture containing 3-(R)-(+)-(1-cyano-1,1-diphenylmethyl)piperidine (0.28 g), 4-hydroxymethylphenethyl bromide (0.22 g), anhydrous potassium carbonate (0.28 g) and acetonitrile (10 ml) was heated under reflux for 5 hours. The mixture was partitioned between dichloromethane (30 ml) and 10% aqueous potassium carbonate (20 ml), the layers separated, and the aqueous layer extracted with dichloromethane (2×20 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%) 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 from acetonitrile to give the title compound as colourless rhombs, yield 0.21 g, m.p. 110°-114° C., {α]D25 +16 2° (c 1.0, CH2Cl2).

Source