Reaction #1528419

Reaction equation

tert-butyl 4-cyanopiperidine-1-carboxylate

2-chloro-3-fluoropyridine

potassium bis(trimethylsilyl)amide

→

desired product

Tert-butyl 4-cyano-4-(3-fluoropyridin-2-yl)piperidine-1-carboxylate

Solvents

toluene

brine

Conditions

Workup

1. 1
   Temperaturecooled in an acetone/ice bath under a nitrogen atmosphere
2. 2
   Otherthe internal temperature below −10° C
3. 3
   Extractionextracted with EtOAc (3×100 ml)
4. 4
   WashThe combined organic extracts were washed with brine (100 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 gel
10. 10
    Washeluted with 10% EtOAc in DCM

Procedure

To a stirred suspension of tert-butyl 4-cyanopiperidine-1-carboxylate (7 g; 33.29 mmol) and 2-chloro-3-fluoropyridine (4.82 g; 36.62 mmol) in toluene (40 ml) cooled in an acetone/ice bath under a nitrogen atmosphere, was added a solution of potassium bis(trimethylsilyl)amide (0.5M in toluene; 79.9 ml; 39.95 mmol) over 30 minutes keeping the internal temperature below −10° C. The reaction mixture was then allowed to warm to ambient temperature with stirring for 2 hours. The reaction was poured into brine (150 ml) and extracted with EtOAc (3×100 ml). The combined organic extracts were washed with brine (100 ml), dried over MgSO4, filtered and evaporated to give a brown oil. The crude product was chromatographed on silica gel eluted with 10% EtOAc in DCM to give the desired product a colourless oil. (4.8 g)

Source