2-Fluoropyridine → Tert-butyl 4-cyano-4-(pyridin-2-YL)piperidine-1-carboxylate

HRID 1501877Notes

Reaction equation

HRID 1501877 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].F[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl-].[NH4+]>O1CCCC1>[C:1]([C:3]1([C:17]2[CH:22]=[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 4

HCID 97462-FluoropyridineHCID 25517Ammonium ChlorideHCID 1514443Tert-butyl 4-cyanopiperidine-1-carboxylateHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

HCID 53439111Tert-butyl 4-cyano-4-(pyridin-2-YL)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-cyanopiperidine-1-carboxylate (0.220 g, 1.05 mmol) and 2-fluoropyridine (0.107 g, 1.10 mmol) in 5 mL of tetrahydrofuran at −78° C. was added sodium bis(trimethylsilyl)amide (1 M solution in diethyl ether, 1.47 mL, 1.47 mmol) dropwise. After 1 hr, the mixture was slowly warmed to ambient temperature, treated with saturated aqueous ammonium chloride, and extracted 3× with dichloromethane. The combined organic extracts were dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-20% ethyl acetate in hexanes, to provide tert-butyl 4-cyano-4-pyridin-2-ylpiperidine-1-carboxylate.

Workup

  1. extractionextracted 3× with dichloromethane
  2. dry with materialThe combined organic extracts were dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified via silica gel chromatography
  6. washeluting with 0-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-68ca7e773e1a48d8a19a7f5f7d86bbfb
Source dataset
uspto-grants-2015_12
Patent number
US09206200B2

Reaction notes

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