Piperidin-4-ol → 1-(1-Methyl-1H-imidazol-2-yl)piperidin-4-ol

HRID 2095745Notes

Reaction equation

[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1Br.[OH:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1>[OH-].[Na+]>[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[N:12]1[CH2:13][CH2:14][CH:9]([OH:8])[CH2:10][CH2:11]1

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of N-methyl-2-bromoimidazole (7.3 g, 45.3 mmol) and 4-hydroxypiperidine (11.4 g, 113 mmol, 2.5 eq) was stirred at 140° C. for 16 h. After cooling to room temperature, the reaction mixture was diluted with 10% aq. NaOH solution to pH 12. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water (20 mL) followed by brine (20 mL), dried over sodium sulfate, filtered, and evaporated under vacuum. The solid residue was purified by column chromatography by eluting with 5% to 20% methanol in dichloromethane to yield the title compound as yellow solid. 1H NMR (CDCl3, 300 MHz): δ=6.64 (d, J=0.9 Hz, 1H), 6.75 (d, J=0.9 Hz, 1H), 3.85-3.84 (m, 1H), 3.47 (s, 3H), 3.24-3.22 (m, 2H), 2.94-2.92 (m, 2H), 2.01-1.98 (m, 2H), 1.71-1.69 (m, 2H). MS (ES+): m/z=182.28 (100) [MH+]. HPLC: tR=0.74 & 1.13 min (verypolar—5 min, ZQ3).

Workup

temperatureAfter cooling to room temperature
customThe organic layer was separated
extractionthe aqueous layer was extracted with ethyl acetate (2×25 mL)
washThe combined organic layers were washed with water (20 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
customevaporated under vacuum
customThe solid residue was purified by column chromatography
washby eluting with 5% to 20% methanol in dichloromethane

Sources & evidence

ORD record: ord-0d639fc5c8d541bc8609ba39c8c92fc2
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445510B2

Reaction notes

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