Sodium hydride → (E)-4-Methyl-1-[1-(4-methyl-2-pyridyl)-4-piperidyl]pent-2-en-1-one

HRID 1775353Notes

Reaction equation

C(OP([CH2:9][C:10]([CH:12]1[CH2:17][CH2:16][N:15]([C:18]2[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][N:19]=2)[CH2:14][CH2:13]1)=[O:11])(OCC)=O)C.[H-].[Na+].[Cl-].[NH4+]>C1COCC1>[CH3:10][CH:12]([CH3:17])/[CH:13]=[CH:9]/[C:10]([CH:12]1[CH2:13][CH2:14][N:15]([C:18]2[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][N:19]=2)[CH2:16][CH2:17]1)=[O:11]

Participants

Conditions

Temperature: 0 °C

Procedure

2-Diethoxyphosphoryl-1-[1-(4-methyl-2-pyridyl)-4-piperidyl]ethanone (product of step B, 350 mg, 1 mmol) was dissolved in anhydrous THF (40 ml) and cooled under argon to 0° C. Sodium hydride (60%, 60 mg, 1.5 mmol) was added and the mixture was stirred at room temperature for 20 minutes. Isobutyryl aldehyde (186 μl, 2 mmol) was added and stirring was continued for 90 minutes. The mixture was poured into saturated ammonium chloride solution (100 ml), the mixture was extracted with DCM, the aqueous layer was extracted again with DCM (2×), and the combined organic phases were dried (sodium sulfate) and concentrated under reduced pressure. The residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile) to yield 30 mg of a brown solid (0.11 mmol, 11%).

Workup

stirringstirring
waitwas continued for 90 minutes
extractionthe mixture was extracted with DCM
extractionthe aqueous layer was extracted again with DCM (2×)
dry with materialthe combined organic phases were dried (sodium sulfate)
concentrationconcentrated under reduced pressure
customThe residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile)

Sources & evidence

ORD record: ord-01d280e8af42484cb77abb9b94627eaa
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260441B2

Reaction notes

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