Reduction of the ester to an alcohol was achieved by DIBAL in toluene.

First hydrogenation of the alkene was done by Pt/C, but the acidic nature of the charcoal cleaved the C-O bond of the alcohol. Some different catalysts were used to achieve the best ratio of trans/cis in the reduced product. The nature of all these were neutral catalysts in a basic solvent to avoid the cleavage of the C-O bond.

PPh3 with CX4 was used to replace the hydroxyl group with a halogen. The Cl replacement was difficult to separate, but Br replacement proved to purify better and had a much higher yield.

The Cl compound proved difficult, with the hemiaminal protecting group being cleaved during flash chromatography even after using pretreated moisture-free silica gel. The Br compound worked up easily, using 80% AcOH to hydrolyze the hemiaminal moiety.

Benzoylation of the alcohol group was achieved by PhCOCL in pyridine and was recrystallized in 4:1 hexane/ether, rendering a white solid ring precursor.

Cyclization was carried out in tetrahydrofuran, utilizing potassium hexamethyldisilzane (KHMDS) as the base. Interestingly, the nature of the halogen or temperature had no effect on yield due to the speed of the reaction. No isolation was done on this step because of the high solubility of the product.

The Boc and benzyl groups were hydrolyzed by 1N HCL at 100 degrees. The hydrochloride was then Fmoc-protected via Schotten-Baumann conditions.

Oxidation of the hydroxymethyl moiety was achieved by Jones reagent in acetone. The final product was 95:5 in favor of the trans configuration.