Hydrogen iodide → 3-Chloro-5-methoxy-4-piperidin-1-ylmethylphenol

HRID 1505890Notes

Reaction equation

I.[Cl:2][C:3]1[CH:15]=[C:14]([O:16]C)[CH:13]=[C:12]([O:18][CH3:19])[C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1>C(=O)([O-])[O-].[Na+].[Na+]>[Cl:2][C:3]1[CH:15]=[C:14]([OH:16])[CH:13]=[C:12]([O:18][CH3:19])[C:4]=1[CH2:5][N:6]1[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1

Participants

Conditions

Temperature: 60 °C

Procedure

Hydroiodic acid (57% solution, 5 mL) was added to 1-(2-chloro-4,6-dimethoxybenzyl)-piperidine (360 mg, 1.3 mol) and the mixture heated at 60° C. for 2 h. The reaction mixture was cooled to ambient temperature, diluted with saturated aqueous sodium carbonate solution (20 mL) and extracted with DCM (3×30 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to afford an beige solid that was then purified by flash chromatography (silica, 12 g column, ISCO, 0-15% (2N ammonia in methanol) in DCM) to afford the title compound as a white solid (277 mg, 88%). 1H NMR (CDCl3, 400 MHz): 6.08 (d, J=2.2 Hz, 1H), 5.96 (d, J=2.2 Hz, 1H), 3.61 (s, 3H), 3.59 (s, 2H), 3.31 (br s, 1H), 2.74-2.64 (m, 4H), 1.70-1.62 (m, 4H), 1.60-1.43 (m, 2H).

Workup

temperatureThe reaction mixture was cooled to ambient temperature
extractionextracted with DCM (3×30 mL)
dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
filtrationfiltered
customevaporated in vacuo
customto afford an beige solid
customthat was then purified by flash chromatography (silica, 12 g column, ISCO, 0-15% (2N ammonia in methanol) in DCM)

Sources & evidence

ORD record: ord-288c28df6e2f4a4d833d49a4eea1d2d3
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216980B2

Reaction notes

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