Tert-butyl 4-cyanopiperidine-1-carboxylate → 1,1-Dimethylethyl 4-(5-chloro-3-fluoro-2-pyridinyl)-4-cyano-1-piperidinecarboxylate

HRID 2422358Notes

Reaction equation

C[Si](C)(C)N[Si](C)(C)C.[K].[Cl:11][C:12]1[CH:13]=[C:14]([F:19])[C:15](F)=[N:16][CH:17]=1.[C:20]([N:27]1[CH2:32][CH2:31][CH:30]([C:33]#[N:34])[CH2:29][CH2:28]1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]>C1(C)C=CC=CC=1>[C:23]([O:22][C:20]([N:27]1[CH2:32][CH2:31][C:30]([C:33]#[N:34])([C:15]2[C:14]([F:19])=[CH:13][C:12]([Cl:11])=[CH:17][N:16]=2)[CH2:29][CH2:28]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

Conditions

Temperature: 0 °C

Procedure

Potassium hexamethyldisilazane (1.34 ml, 0.5 M solution in toluene) was slowly added to a solution of 5-Chloro-2,3-difluoro-pyridine (0.1 g) and N-Boc-4-Cyano-Piperidine (0.14 g) in 3 ml toluene at 0° C., under nitrogen. The mixture was stirred at 0° C. for 1 hr. After cooling, the reaction mixture was quenched in 1N HCl. The aqueous phase was extracted twice with ethyl acetate and the combined organic were washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by chromatography [SiO2; hexane-ethyl acetate-hexane (4:1)] to give 111 mg (49%) of 5-chloro-4′-cyano-3-fluoro-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert -butyl ester; MS (ES+) 240 (M-Boc+H+).

Workup

temperatureAfter cooling
customthe reaction mixture was quenched in 1N HCl
extractionThe aqueous phase was extracted twice with ethyl acetate
washthe combined organic were washed with water
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customThe crude product was purified by chromatography [SiO2; hexane-ethyl acetate-hexane (4:1)]

Sources & evidence

ORD record: ord-686399241fda4d8eb525165a4f82fcf1
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07960401B2

Reaction notes

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