Iodoethane → 1-Benzyl-3-ethylpiperidin-4-one

HRID 2054825Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].I[CH2:26][CH3:27]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([CH2:26][CH3:27])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a −78° C. solution of 1-benzyl-piperidin-4-one (3.79 g, 20 mmol) in anhydrous THF (20 mL) was added lithium hexamethyldisilazide (21 mL, 21 mmol of a 1.0 M solution in THF). After being stirred at −78° C. for 30 min, a solution of iodoethane (1.7 mL, 21 mmol) in THF (5 mL) was added to the reaction mixture. The resultant solution was stirred at 25° C. for 2 h and quenched with water. The aqueous layer was extracted with CH2Cl2. The organic extracts were combined, washed with brine and dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude product. The crude material was purified by flash column chromatography (hexane/EtOAc) to provide 0.51 g (11.5% yield) of 1-benzyl-3-ethyl-piperidin-4-one, which was converted into 1-benzyl-3-ethyl-piperidin-4-ylamine (3) using the same procedure as in Scheme 1-1. ((±)-cis:(±)-trans=1:1) LCMS m/z: 219 (M+H)+. This material was used without further purification.

Workup

customquenched with water
extractionThe aqueous layer was extracted with CH2Cl2
washwashed with brine
dry with materialdried over MgSO4
filtrationThe solution was filtered
concentrationconcentrated in vacuo
customto give the crude product
customThe crude material was purified by flash column chromatography (hexane/EtOAc)

Sources & evidence

ORD record: ord-fd5e0bf60688484e8fea4600a5fb464f
Source dataset: uspto-grants-2008_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07329755B2

Reaction notes

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