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

HRID 1169824Notes

Reaction equation

HRID 1169824 reaction equation
F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[C:8]([CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1)#[N:9].C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1(C)C=CC=CC=1.[Cl-].[Na+].O>[C:8]([C:10]1([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1)#[N:9]

Participants

6

Reactant 3

HCID 97462-FluoropyridineHCID 1514443Tert-butyl 4-cyanopiperidine-1-carboxylateHCID 3251421Potassium bis(trimethylsilyl)amide

Product 1

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

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 2-fluoro-pyridine (5.83 g, 60 mmole) in toluene (40 mL) was added tert-butyl 4-cyanopiperidine-1-carboxylate (I-1) (4.22 g, 20 mmole) and 0.5M solution of KHMDS (48 mL, 24 mmole). The reaction mixture was stirred 2 h at rt ° C. After this time, LCMS indicated that the reaction was completion. The reaction mixture was poured into brine (150 mL) and extracted with EtOAc (3×150 mL). The combined organic extracts were washed with brine (2×100 mL), dried over MgSO4, filtered and concentrated to afford the desired product tert-butyl 4-cyano4-pyridin-2-ylpiperidine-1-carboxylate (I-2) as a yellow-brown solid. Analytical LCMS: single peak (214 mm), 3.076 min. This product was used in next step reaction without further purification.

Workup

  1. extractionextracted with EtOAc (3×150 mL)
  2. washThe combined organic extracts were washed with brine (2×100 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-060b496a48b74d938558cfeddc99d528
Source dataset
uspto-grants-2010_11
Patent number
US07825135B2

Reaction notes

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