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

HRID 407178Notes

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+]>C1COCC1>[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

Conditions

Temperature: -78 °C

Procedure

A mixture of tert-butyl 4-cyanopiperidine-1-carboxylate (220 mg, 1.05 mmol) and 2-fluoropyridine (0.094 mL, 1.10 mmol) was dissolved in 5.2 mL of THF. The reaction was purged with a stream of nitrogen and cooled to −78° C. To this reaction was added sodium bis(trimethylsilyl)amide (1.0 M in THF, 1.47 mL, 1.47 mmol), which was stirred for 1 h. The reaction was warmed to ambient temperature, stirred for 1 hour, and quenched with a saturated ammonium chloride solution. The mixture was extracted with dichloromethane (3×10 mL). The combined organic extracts were dried over sodium sulfate, filtered, concentrated, and subjected to silica gel chromatography eluting with 0-20% ethyl acetate in hexanes to provide tert-butyl 4-cyano-4-pyridin-2-ylpiperidine-1-carboxylate.

Workup

customThe reaction was purged with a stream of nitrogen
temperatureThe reaction was warmed to ambient temperature
stirringstirred for 1 hour
customquenched with a saturated ammonium chloride solution
extractionThe mixture was extracted with dichloromethane (3×10 mL)
dry with materialThe combined organic extracts were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
washeluting with 0-20% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-c358c2917e254a31a442f89870e78f16
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754220B2

Reaction notes

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