Sodium hydride → 2-Bromo-3-cyano-4-(4-phenylpiperidinyl)pyridine

HRID 1428488Notes

Reaction equation

[H-].[Na+].[C:3]1([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:15][C:16]1[N:23]=[CH:22][CH:21]=[C:20](Br)[C:17]=1[C:18]#[N:19]>CN(C=O)C>[Br:15][C:16]1[C:17]([C:18]#[N:19])=[C:20]([N:12]2[CH2:11][CH2:10][CH:9]([C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH2:14][CH2:13]2)[CH:21]=[CH:22][N:23]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of NaH (0.146 g, 3.818 mmol, 60%) in DMF (20 ml) cooled at 0° C. was added 4-phenylpiperidine (0.616 g, 3.818 mmol). The resulting mixture was stirred for 5 min., then compound D1 (1 g, 3.016 mmol) was added. The resulting reaction mixture was stirred for 1 h. The reaction mixture was then quenched with NH4Cl (aqueous sat. solution) and extracted with Et2O. The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH gradient as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D6 (0.985 g, 75%).

Workup

customThe resulting reaction mixture
stirringwas stirred for 1 h
customThe reaction mixture was then quenched with NH4Cl (aqueous sat. solution)
extractionextracted with Et2O
customThe organic layer was separated
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
customThe crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH gradient as eluent)
customThe desired fractions were collected
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-008bd79b5c9f47d3bf2f693777310335
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08937060B2

Reaction notes

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