Potassium Carbonate → 1-Benzyl-4-[5-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine

HRID 419712Notes

Reaction equation

Cl.Cl.[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([C:16]([NH2:18])=[NH:17])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:25][C:26]1[CH:27]=[C:28]([CH:33]=[CH:34][C:35]=1[F:36])[C:29](=O)[CH2:30]Br>CN(C)C=O.C(OCC)(=O)C>[CH2:3]([N:10]1[CH2:11][CH2:12][CH:13]([C:16]2[NH:18][C:29]([C:28]3[CH:33]=[CH:34][C:35]([F:36])=[C:26]([Cl:25])[CH:27]=3)=[CH:30][N:17]=2)[CH2:14][CH2:15]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

Conditions

Temperature: 45 °C

Procedure

Dissolve 1-benzyl-piperidine-4-carboxamidine dihydrochloride (2 g; 1.00 equiv; 6.89 mmoles) in dimethylformamide (90 mL). Add powdered potassium carbonate (4 equiv; 27.56 mmoles; 3.8095 g) and warm to ˜45° C. Add 3-chloro-4-fluoro-phenacyl bromide (2.00 equiv; 13.782 mmoles; 3.5366 g) in 8 mL with DMF dropwise over 40 minutes. Dilute with 50 mL ethyl acetate, stir 5 min and filter. Evaporate and partition with ethyl acetate/sat. sodium bicarbonate, wash organic layer with water, then saturated aqueous sodium chloride. Dry with MgSO4, filter and evaporate to red foam. Purify over flash silica gel with 0-10% MeOH/ACN. Pool fractions to give 1.9772 g (5.346 mmol, 78%) 1-Benzyl-4-[5-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine.

Workup

filtrationfilter
customEvaporate
custompartition with ethyl acetate/
washsodium bicarbonate, wash organic layer with water
dry with materialDry with MgSO4
filtrationfilter
customevaporate to red foam
customPurify over flash silica gel with 0-10% MeOH/ACN

Sources & evidence

ORD record: ord-b2e0556a4b61428b852846c57bac4a2b
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093383B2

Reaction notes

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