1-Methyl-4-piperidone → 5-Chloro-2-(4-hydroxy-1-methylpiperidin-4-yl)benzothiophene

HRID 1457019Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.C([Li])CCC.[CH3:16][N:17]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([C:20]3([OH:23])[CH2:21][CH2:22][N:17]([CH3:16])[CH2:18][CH2:19]3)=[CH:7][C:6]=2[CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 0.300 gm (1.78 mMol) 5-chlorobenzothiophene in 20 mL tetrahydrofuran was cooled to -78° C. To the cooled solution was then added 1.27 mL (1.78 mMol) n-butyllithium (1.2M in tetrahydrofuran) and the reaction mixture stirred for 1 hour after the addition was complete. To this solution was added 0.218 mL (1.78 mMol) 1-methyl-4-piperidone and the reaction mixture was allowed to warm to 0° C. The reaction mixture was quenched with saturated aqueous sodium bicarbonate and partitioned by the addition of hexane/diethyl ether. The organic phase was washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure to provide 0.34 gm of a tan solid. This residue was subjected to silica gel chromatography, eluting with chloroform containing 5% methanol. Fractions containing product were combined and concentrated under reduced pressure to provide 0.34 gm (68%) of the title compound as an off-white solid.

Workup

additionafter the addition
customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate
custompartitioned by the addition of hexane/diethyl ether
washThe organic phase was washed with saturated aqueous sodium chloride
dry with materialdried over sodium sulfate
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-11b690607cbe4ca9816d8a04006249ff
Source dataset: uspto-grants-1998_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05846982

Reaction notes

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