Methanol → 1-Methoxy-4-methylamino-piperidine-4-carboxylic acid methyl ester
Reaction equation
Cl.[CH3:2][O:3][N:4]1[CH2:9][CH2:8][C:7]([NH:13][CH3:14])([C:10]([OH:12])=[O:11])[CH2:6][CH2:5]1.S(Cl)(Cl)=O.[CH3:19]O>>[CH3:19][O:11][C:10]([C:7]1([NH:13][CH3:14])[CH2:8][CH2:9][N:4]([O:3][CH3:2])[CH2:5][CH2:6]1)=[O:12]Participants
Procedure
To a suspension of 1-methoxy-4-methylamino-piperidine-4-carboxylic acid hydrochloride salt (2.08 g, 9.26 mmol) in methanol (20 ml) at 0-5° C. was added thionyl chloride (2.41 ml, 3.97 g, 33.40 mmol) and the reaction mixture was heated at reflux for 7 days. After cooling, the mixture was concentrated, the residue diluted with ice water and neutralised with aqueous sodium bicarbonate. The aqueous phase was extracted with ethyl acetate (4×), the combined organic layers washed with brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (gradient ethyl acetate→ethyl acetate/methanol 20:1). Yield: 76 mg of 1-methoxy-4-methylamino-piperidine-4-carboxylic acid methyl ester (title compound P5.4) as an oil.
Workup
- temperaturethe reaction mixture was heated
- temperatureat reflux for 7 days
- temperatureAfter cooling
- concentrationthe mixture was concentrated
- additionthe residue diluted with ice water and neutralised with aqueous sodium bicarbonate
- extractionThe aqueous phase was extracted with ethyl acetate (4×)
- washthe combined organic layers washed with brine
- dry with materialdried over sodium sulfate
- concentrationconcentrated
- customThe residue was purified by chromatography on silica gel (gradient ethyl acetate→ethyl acetate/methanol 20:1)
Sources & evidence
- ORD record
- ord-0bcef22479a64fc28b08471dcc3585bf
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09023760B2
Reaction notes
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