Tetrahydrofuran → HCID 23194322, compound
Reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])(C)C)=[O:10])[CH2:5][CH2:4]1)#[N:2].F[C:17]1[CH:22]=[C:21]([CH3:23])C=CN=1.[CH3:24][Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl-].[NH4+:35].[CH2:36]1COC[CH2:37]1>>[C:24]([C:3]1([C:1]2[CH:17]=[CH:22][CH:21]=[CH:23][N:2]=2)[CH2:4][CH2:5][N:6]([C:9]([O:11][CH2:12][CH2:15][CH2:36][CH3:37])=[O:10])[CH2:7][CH2:8]1)#[N:35]Participants
Conditions
- Temperature
- 78 °C
Procedure
tert-Butyl 4-cyanopiperidine-1-carboxylate (0.220 g, 1.05 mmol) and 2-fluoro-4-methylpyridine (0.107 g, 1.10 mmol, 1.05 equiv) were suspended in THF (5 mL), cooled to 78° C., and treated with sodium bis(trimethylsilyl)amide (1 M solution in diethyl ether, 1.47 mL, 1.47 mmol, 1.40 equiv) dropwise. After 1 hour, the mixture was warmed to ambient temperature, treated with saturated aqueous ammonium chloride, and extracted with dichloromethane (3×). The combined organic extracts were dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (100:0 to 4:1 hexanes:ethyl acetate), providing Cert-butyl 4-cyano-4-pyridin-2-ylpiperidine-1-carboxylate. The resulting clear oil was suspended in ethyl acetate (5 mL), cooled to 0° C. and saturated with gaseous hydrogen chloride. The mixture was warmed to ambient temperature and after 18 hours, was concentrated in vacuo, providing the titled compound.
Workup
- temperaturethe mixture was warmed to ambient temperature
- extractionextracted with dichloromethane (3×)
- dry with materialThe combined organic extracts were dried with sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified by silica gel chromatography (100:0 to 4:1 hexanes:ethyl acetate)
Sources & evidence
- ORD record
- ord-17cb0d27fcab45d59d5fbd75e32d5221
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08507494B2
Reaction notes
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