METHOD FOR PRODUCING ALKYL CIS-4-AMINO-3- METHOXY-1-PIPERIDINE CARBOXYLATE HYDROCHLORIDE

摘要

PURPOSE: A method for producing alkyl cis-4-amino-3- methoxy-1-piperidine carboxylate hydrochloride is provided, thereby the titled compound having high purity can be easily produced because the further purification steps are not required and the production is performed under the mild conditions. CONSTITUTION: The method for producing alkyl cis-4-amino-3- methoxy-1-piperidine carboxylate hydrochloride represented by formula (I) comprises the steps of: reacting alkyl trans-4-bromo-3- hydroxypiperidine-1-carboxylate of formula (III) with benzoyl isocyanate in organic solvents to produce alkyl trans-4-bromo-3- benzoylaminocarbonyloxy-1-piperidine carboxylate of formula (IV); adding base such as kalium tert-butoxide into the compound of formula (IV) to produce alkyl cis-1-benzoyl-2-oxo- hexahydro-oxazolo(5,4,c) pyridine-5-carboxylate of formula (V); reacting the compound of formula (V) with lithium hydroxide·H2O to produce alkyl cis-2-oxo-hexahydro-oxazolo(5,4-c) pyridine-5-carboxylate of formula (VI); reacting the compound of formula (VI) with triethylamine, di-tert-butoxy dicarbonate, and dimethylaminopyridine to produce cis-1-tert- butoxycarbonyl-5- ethoxycarbonyl-2-oxo- hexahydro- oxazolo(5,4-c) pyridine of formula (VII); reacting the compound of formula (VII) with cesium carbonate to produce alkyl cis-4-tert- butoxycarbonyl amino-3-hydroxy-1-piperidine carboxylate of formula (VIII); adding sodium hydroxide, dimethyl sulfate, and benzyltriethyl ammonium chloride into the compound of formula (VIII) to produce alkyl cis-4-tert-butoxycarbonylamino- 3-methoxy-1-piperidine carboxylate of formula (IX); and adding hydrogen chloride dissolved organic solvent into the compound of formula (IX) to produce alkyl cis-4-amino-3- methoxy-1-piperidine carboxylate hydrochloride of formula (I).