Tert-butyl 4-cyanopiperidine-1-carboxylate → Tert-butyl 4-cyano-4-(4-methylpyridin-2-yl)piperidine-1-carboxylate

HRID 2380862Notes

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]=[C:21]([CH3:23])[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]=[C:21]([CH3:23])[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 (15.2 g, 72.3 mmol) and 2-fluoro-4-methylpyridine (9.64 g, 87.0 mmol) was dissolved in 361 mL of THF. The reaction was purged with a stream of nitrogen and cooled to −78° C. To this reaction was added 1.0 M sodium bis(trimethylsilyl)amide in THF (101 mL, 101 mmol), which was stirred for 1 hour. The reaction was warmed to ambient temperature, stirred for 36 hours, and quenched with a saturated ammonium chloride solution. The mixture was extracted with dichloromethane (3×200 mL). The combined organic extracts were dried over sodium sulfate, filtered, concentrated, and subjected to silica gel chromatography eluting with 0-25% EtOAc in hexanes to yield tert-butyl 4-cyano-4-(4-methylpyridin-2-yl)piperidine-1-carboxylate.

Workup

customThe reaction was purged with a stream of nitrogen
temperatureThe reaction was warmed to ambient temperature
stirringstirred for 36 hours
customquenched with a saturated ammonium chloride solution
extractionThe mixture was extracted with dichloromethane (3×200 mL)
dry with materialThe combined organic extracts were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
washeluting with 0-25% EtOAc in hexanes

Sources & evidence

ORD record: ord-22cff14dae6440b78158b60f86a7c081
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258135B2

Reaction notes

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