1367879-28-4

Upstream product

• 6099-04-3 trans-3-methoxycinnamic acid 
• 125617-35-8 (E)-3-(3-Methoxyphenyl)-2-propen-1-ol 
• 1384457-47-9 (2R,3R)-3-(3-methoxyphenyl)-2-methylpent-4-enoic acid (R)-1-phenylethylamine salt 
• 1367879-31-9 (2R,3R)-3-(3-methoxyphenyl)-2-methylpent-4-enoic acid 
• 1367879-30-8 (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpent-4-eneamide 
• 1367879-29-5 (2R,3R)-3-(3-methoxyphenyl)-2-methylpent-4-enoyl chloride 
• 15851-92-0 (E)-3-methoxycinnamoyl chloride 

Downstream Products

• 175591-09-0 tapentadol hydrochloride 
• 175591-22-7 (βR,γR)-γ-ethyl-N,N,β-trimethyl-3-methoxybenzenepropanamine 

Relevant academic research and scientific papers

Method for the preparation of 1-aryl-1-alkyl-3-dialkylaminopropane compounds

The present invention refers to the preparation of 1-aryl-1-alkyl-2-alkyl-3-dialkylamino-propane compounds, such as tapentadol, using a diastereoselective Eschenmoser-Claisen or Ireland-Claisen rearrangement.

O-SUBSTITUTED (2R,3R)-3-(3-HYDROXYPHENYL)-2-METHYL-4-PENTENOIC ACIDS AND A METHOD OF OBTAINING THE SAME

The compounds of general formula II are new and represent important intermediates in the synthesis of tapentadol. In the synthesis of tapentadol of formula I and its pharmaceutically acceptable salts, O-protected (2R,3R)-acids of general formula II, in step A, are reacted in an inert organic solvent with an activating agent, optionally in presence of a catalyst or a base; in step B, the obtained compounds of general formula V, wherein R has the above mentioned meaning and X stands for chlorine or alkoxycarbonyloxyl group O-CO-OR1 or pivaloyloxyl O-CO-t-Bu group, wherein R1 is methyl or ethyl, are reacted with dimethylamine or its salts optionally in presence of a base; in step C, the obtained N, N-dimethylamides of general formula VI, wherein R has the above mentioned meaning, are reduced by means of hydride agents in a suitable solvent; in step D, the produced alkeneamines of general formula VII, wherein R has the above mentioned meaning, are hydrogenated on a metal catalysts in a suitable solvent; and, finally, in step E, the produced alkaneamines of general formula VIII, wherein R has the above mentioned meaning, are O-dealkylated by means of dealkylating agents, and, if required, the obtained tapentadol is converted by the action of a pharmaceutically acceptable acid to respective salts, e.g. hydrochloride.