The chiral precursor (IV) was obtained by two alternative procedures. Addition of cyclopentylmagnesium bromide (II) to ethyl phenylglyoxylate (I) afforded the racemic hydroxyester (III). Basic hydrolysis of the ethyl ester group of (III) gave the corresponding carboxylic acid, which was resolved using cinchonidine.

An alternative asymmetric procedure consisted in the LDA-promoted addition of cyclopentenone (VI) to the chiral dioxolanone (V), followed by catalytic hydrogenation to furnish (VII). The dioxolane group of (VII) was then cleaved by basic hydrolysis yielding the target (R)-hydroxyacid (IV).

The alkylation of 4-(tert-butoxycarbonylamino)piperidine (VIII) with (S)-4- methylhexyl methanesulfonate (IX) provided the tertiary amine (X). Cleavage of the Boc protecting group of (X) gave aminopiperidine (XI), which was finally coupled with the chiral hydroxyacid (IV) by means of carbonyl diimidazole.

The chiral precursor (IV) was obtained by two alternative procedures. Addition of cyclopentylmagnesium bromide (II) to ethyl phenylglyoxylate (I) afforded the racemic hydroxyester (III). Basic hydrolysis of the ethyl ester group of (III) gave the corresponding carboxylic acid, which was resolved using cinchonidine.

An alternative asymmetric procedure consisted in the LDA-promoted addition of cyclopentenone (VI) to the chiral dioxolanone (V), followed by catalytic hydrogenation to furnish (VII). The dioxolane group of (VII) was then cleaved by basic hydrolysis yielding the target (R)-hydroxyacid (IV).

The alkylation of 4-(tert-butoxycarbonylamino)piperidine (VIII) with 5-bromo-2-methyl-2-pentene (IX) provided the tertiary amine (X). Cleavage of the Boc protecting group of (X) gave aminopiperidine (XI), which was finally coupled with the chiral hydroxyacid (IV) by means of carbonyl diimidazole.

The chiral precursor (IV) was obtained by two alternative procedures. Addition of cyclopentylmagnesium bromide (II) to ethyl phenylglyoxylate (I) afforded the racemic hydroxyester (III). Basic hydrolysis of the ethyl ester group of (III) gave the corresponding carboxylic acid, which was resolved using cinchonidine.

In a related procedure, hydroxyacid (IV) was coupled with 1-Boc-4-aminopiperidine (XII) employing EDC and HOBt to give amide (XIII). Acid cleavage of the Boc group of (XIII) yielded amine (XIV), that was finally alkylated with mesylate (IX).

The chiral precursor (IV) was obtained by two alternative procedures. Addition of cyclopentylmagnesium bromide (II) to ethyl phenylglyoxylate (I) afforded the racemic hydroxyester (III). Basic hydrolysis of the ethyl ester group of (III) gave the corresponding carboxylic acid, which was resolved using cinchonidine.

In a related procedure, hydroxyacid (IV) was coupled with 1-Boc-4-aminopiperidine (XII) employing EDC and HOBt to give amide (XIII). Acid cleavage of the Boc group of (XIII) yielded amine (XIV), that was finally alkylated with bromide (IX).