The nitrosation of hexahydrophenalenone oxime (I) by means of NaNO2 and H2SO4 produced the N-nitroimine (II). Condensation of this intermediate with 1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (III) in acetonitrile in the presence of molecular sieves gave rise to enamine (IV), which was finally reduced to the title amine using NaBH3CN.

The Stobbe-type condensation of tetralone (I) with diethyl succinate (II) by means of potassium tert-butoxide in tert butanol and subsequent hydrolysis/decarboxylation in HOAc/HCl gives the propionic acid (III), which is asymmetrically reduced with H2 over a chiral ruthenium catalyst in methanol to afford (S)-3-(1,2,3,4-tetrahydronaphthalen-1-yl)propionic acid (S)-(IV). The cyclization of (IV) by means of PPA at 130 C provides the hexahydrophenalen-1-one (V), which by reaction with hydroxylamine is converted into the oxime (VI). The reduction of (VI) with H2 over Raney Ni in methanol yields the corresponding amine (VII), which is condensed with the piperidinium iodide (VIII) by means of K2CO3 in refluxing ethanol to afford a diastereomeric mixture from which the desired enantiomer (IX) is separated by column chromatography. A Strecker reaction of (IX) with aniline and Tms-CN in HOAc gives the anilino nitrile (X), which is finally cyclized by reaction with formic acid, Ac2O and formamide at 200 C to yield the target spiro compound. Alternatively, the anilino nitrile (X) is hydrolyzed with formic acid/Ac2O to give the formylated carboxamide (XI), which is finally cyclized with refluxing triethyl orthoformate, followed by reduction with NaBH4 in methanol.