Hydrochloric Acid → 4-{[2-(2,5-Dimethyl-phenyl)-acetyl]-methyl-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester

HRID 1473767Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1([NH:13][CH3:14])[CH2:10][CH2:9][N:8]([O:11][CH3:12])[CH2:7][CH2:6]1)=[O:4].[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:17]=1[CH2:23][C:24](Cl)=[O:25].Cl>N1C=CC=CC=1.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1([N:13]([C:24](=[O:25])[CH2:23][C:17]2[CH:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]=2[CH3:15])[CH3:14])[CH2:10][CH2:9][N:8]([O:11][CH3:12])[CH2:7][CH2:6]1)=[O:4]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 1-methoxy-4-methylamino-piperidine-4-carboxylic acid methyl ester (200 mg, 0.99 mmol) in pyridine (5 ml) was added (2,5-dimethyl-phenyl)-acetyl chloride (240 mg, 1.31 mmol) dropwise at 0° C. The reaction mixture was stirred at 0° C. for one hour and at room temperature for 6 hours, poured on ice water, acidified to pH 7 with an aqueous 2N HCl solution and diluted with ethyl acetate (50 ml). The layers were separated, the aqueous phase extracted with ethyl acetate (3×25 ml), the combined organic phases washed with water (3×15 ml) and brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 2:1). Yield: 170 mg of 4-{[2-(2,5-dimethyl-phenyl)-acetyl]-methyl-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester (title compound P4.46) as a colorless gum.

Workup

additionpoured on ice water
customThe layers were separated
extractionthe aqueous phase extracted with ethyl acetate (3×25 ml)
washthe combined organic phases washed with water (3×15 ml) and brine
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 2:1)

Sources & evidence

ORD record: ord-16fbcfd7104745528113a9822aef343a
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018135B2

Reaction notes

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