Imidazole → 1-[(2-Imidazol-1-yl)acetyl]-4-(2,3,4,5,6-pentafluorophenoxy)piperidine

HRID 1613212Notes

Reaction equation

[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.Cl[CH2:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[C:22]([F:23])=[C:21]([F:24])[C:20]([F:25])=[C:19]([F:26])[C:18]=2[F:27])[CH2:12][CH2:11]1)=[O:9].O>CN(C)C=O>[N:1]1([CH2:7][C:8]([N:10]2[CH2:11][CH2:12][CH:13]([O:16][C:17]3[C:18]([F:27])=[C:19]([F:26])[C:20]([F:25])=[C:21]([F:24])[C:22]=3[F:23])[CH2:14][CH2:15]2)=[O:9])[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

Conditions

Temperature: 75 °C

Procedure

A stirring solution of 7.11 g of imidazole in 100 ml of dimethylformamide was treated with a solution of 7.22 g of 1-(2-chloroacetyl)-4-(2,3,4,5,6-pentafluorophenoxy)piperidine in 50 ml of dimethylformamide and then stirred at 75° C. for five hours. After cooling, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water followed by a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated to an oil. The oil was purified by means of high pressure liquid chromatography (silica gel; elution with 7.5% methanol/dichloromethane). Recrystallization of the resulting solid from ethyl acetate/hexane (10:1) afforded 3.70 g (47.0%) of 1-[(2-imidazol-1-yl)acetyl]-4-(2,3,4,5,6-pentafluorophenoxy)piperidine, m.p. 95°-96° C.

Workup

temperatureAfter cooling
extractionextracted with ethyl acetate
washThe organic layer was washed with water
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
concentrationconcentrated to an oil
customThe oil was purified by means of high pressure liquid chromatography (silica gel; elution with 7.5% methanol/dichloromethane)
customRecrystallization of the resulting solid from ethyl acetate/hexane (10:1)

Sources & evidence

ORD record: ord-c3bf87d969554d5095c96651d023fb7a
Source dataset: uspto-grants-1993_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05192776

Reaction notes

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