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

HRID 587627Notes

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-5a0c138a2ad7453b9c8ba5e2182b1e85
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09226930B2

Reaction notes

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