Ethylene Glycol → 1-[5-Chloro-3-(4-hydroxypiperidin-1-yl)-2-methoxy-4-methylphenyl]ethanone

HRID 510873Notes

Reaction equation

[Cl:1][C:2]1[C:3]([CH3:14])=[C:4](I)[C:5]([O:11][CH3:12])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[OH:15][CH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C(O)CO.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(O)(C)C.[Cu]I.O>[Cl:1][C:2]1[C:3]([CH3:14])=[C:4]([N:19]2[CH2:20][CH2:21][CH:16]([OH:15])[CH2:17][CH2:18]2)[C:5]([O:11][CH3:12])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of 1-(5-chloro-3-iodo-2-methoxy-4-methylphenyl)ethanone (150 mg, 0.46 mmol) and 4-hydroxypiperidine (56 mg, 0.56 mmol) in isopropyl alcohol (1 mL) was added 1,2-ethanediol (0.052 mL, 0.92 mmol), potassium phosphate (200 mg, 0.93 mmol), and copper(I) iodide (5 mg, 0.02 mmol). The reaction was heated at 80° C. overnight and then cooled to room temperature. Water was added, and the mixture was extracted with ethyl acetate. The combined organic phases were washed with brine and dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified on silica gel, eluting with 0 to 50% ethyl acetate in hexanes, to give the desired product (15 mg, 11%). LCMS calculated for C15H21ClNO3 (M+H)+: m/z=298.1. found: 298.0.

Workup

temperaturecooled to room temperature
extractionthe mixture was extracted with ethyl acetate
washThe combined organic phases were washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated to dryness
customThe residue was purified on silica gel
washeluting with 0 to 50% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-26acb8478a754a1c84d29b4280ca02fb
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096600B2

Reaction notes

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