5,6,7,8-Tetrahydro-1-naphthalenecarboxylic acid → 135729-78-1

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Reaction Steps

The synthetic route for preparing palonosetron is described in U.S. Pat. No. 5,202,333, wherein 5,6,7,8-tetrahydro-1-naphthalenecarboxylic acid (Compound II) is reacted with (S)-3-amino-1-azabicyclo[2.2.2]octane (Compound III) to obtain (S)—N-(1-azabicyclo-[2.2.2]oct-3-yl)-5,6,7,8-tetrahydro-1-naphthalenecarboxamide (Compound IV), which is recrystallized from a mixture of ethyl acetate and hexane. Reaction of Compound IV with n-butyl lithium in hexane in presence of dimethylformamide (DMF) affords (S)-2-(1-azabicyclo-[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro-1H-benz[de]isoquinolin-1-one (Compound V), and treatment of Compound V using palladium hydroxide on carbon with hydrogen affords a diastereomeric mixture containing 98.9% of Compound A. This process is depicted in Scheme 1 below.

Provenance & Evidence