Reaction #1528416

Reaction equation

lithium diisopropylamide

tert-butyl 4-cyanopiperidine-1-carboxylate

(bromomethyl)cyclopropane

→

title product

Tert-butyl 4-cyano-4-(cyclopropylmethyl)piperidine-1-carboxylate

Solvents

brine

THF

THF

THF

Conditions

Workup

1. 1
   workup.STIRRINGThe solution was stirred at −70° C. for 1 hour
2. 2
   Temperatureto warm to ambient temperature over 2 hours
3. 3
   Extractionextracted with EtOAc (3×200 ml)
4. 4
   WashThe combined organic extracts were washed with brine (200 ml)
5. 5
   Dryingdried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Otherevaporated
8. 8
   Otherto give a brown oil
9. 9
   OtherThe crude product was chromatographed on silica
10. 10
    Washeluted with 5% EtOAc in isohexane

Procedure

To a stirred solution of lithium diisopropylamide (2M solution in THF; 60 ml; 0.12 mol) in THF (60 ml) at −70° C. was added tert-butyl 4-cyanopiperidine-1-carboxylate (21 g; 0.1 mol) in THF (150 ml) over 1 hour. The mixture was stirred at −70° C. for 1 hour and then (bromomethyl)cyclopropane (17.53 g; 0.13 mol) in THF (20 ml) was added. The solution was stirred at −70° C. for 1 hour then allowed to warm to ambient temperature over 2 hours. The reaction was poured into brine (150 ml) and extracted with EtOAc (3×200 ml). The combined organic extracts were washed with brine (200 ml), dried over MgSO4, filtered and evaporated to give a brown oil. The crude product was chromatographed on silica eluted with 5% EtOAc in isohexane to give the title product as a colourless oil. (24.8 g)

Source