Tert-butyl 4-cyanopiperidine-1-carboxylate → HCID 57425760, compound

HRID 1441237Notes

Reaction equation

HRID 1441237 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2].Cl[C:17]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][N:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1(C)C=CC=CC=1.[Cl-].[Na+].O>[C:1]([C:3]1([C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2]

Participants

6

Reactant 3

HCID 1514443Tert-butyl 4-cyanopiperidine-1-carboxylateHCID 27827912-Chloro-3-fluoropyridineHCID 3251421Potassium bis(trimethylsilyl)amide

Product 1

HCID 57425760HCID 57425760, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

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)

Workup

  1. temperaturecooled in an acetone/ice bath under a nitrogen atmosphere
  2. customthe internal temperature below −10° C
  3. extractionextracted with EtOAc (3×100 ml)
  4. washThe combined organic extracts were washed with brine (100 ml)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give a brown oil
  9. customThe crude product was chromatographed on silica gel
  10. washeluted with 10% EtOAc in DCM

Sources & evidence

ORD record
ord-a7e554874dc144d1817af299f5f0690f
Source dataset
uspto-grants-2010_02
Patent number
US07655644B2

Reaction notes

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