Potassium Carbonate → 4-[4-Hydroxy-4-(4-methyl-benzyl)-piperidin-1-yl]-1-(4-methoxy-phenyl)-butan-1-one

HRID 507268Notes

Reaction equation

Cl[CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)=[O:6].[CH3:15][C:16]1[CH:29]=[CH:28][C:19]([CH2:20][C:21]2([OH:27])[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[CH:18][CH:17]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[OH:27][C:21]1([CH2:20][C:19]2[CH:18]=[CH:17][C:16]([CH3:15])=[CH:29][CH:28]=2)[CH2:26][CH2:25][N:24]([CH2:2][CH2:3][CH2:4][C:5]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=2)=[O:6])[CH2:23][CH2:22]1

Participants

Conditions

Temperature: 107.5 °C

Procedure

A mixture of 1.62 g of 4-chloro-1-(4-methoxy-phenyl)-butan-1-one (1), 1.20 g of 4-(4-methyl-benzyl)-piperidin-4-ol (2), 1.62 g of K2CO3, and 0.49 g of KI in acetonitrile (30 mL) was stirred and refluxed at 105 to 110° C. for 9 hours under nitrogen atmosphere. After the solvent was removed, ice water was added and the mixture was extracted with ethyl acetate. The organic layer was successively washed with water and brine and dried over MgSO4. After the solvent was removed, the obtained oily residue was purified by silica gel chromatography (chloroform:methanol=20/1 to 10/1) and the purified product was recrystallized from AcOEt/Et2O to afford 1.73 g of compound (3).

Workup

customAfter the solvent was removed
additionice water was added
extractionthe mixture was extracted with ethyl acetate
washThe organic layer was successively washed with water and brine
dry with materialdried over MgSO4
customAfter the solvent was removed
customthe obtained oily residue was purified by silica gel chromatography (chloroform:methanol=20/1 to 10/1)
customthe purified product was recrystallized from AcOEt/Et2O

Sources & evidence

ORD record: ord-bedd0e60b188490b9c21bc181597928e
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786140B2

Reaction notes

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