反应详情

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.

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 7 days
3. temperatureAfter cooling
4. concentrationthe mixture was concentrated
5. additionthe residue diluted with ice water and neutralised with aqueous sodium bicarbonate
6. extractionThe aqueous phase was extracted with ethyl acetate (4×)
7. washthe combined organic layers washed with brine
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated
10. customThe residue was purified by chromatography on silica gel (gradient ethyl acetate→ethyl acetate/methanol 20:1)