A patent (Ref. 1) published in 2017 disclosed the most recent synthesis of oteseconazole, featuring an asymmetric Henry reaction to install the tertiary hydroxy group. Dibromo pyridine 2 was used as the starting point. Eto-Ashwood reductive coupling of 2 and bromodifluoroacetate 3 eliminated two bromides to give ester 4 with Cu powder as the reducing agent in DMSO. By the treatment of morpholine 5, the ester 4 was converted to Weinreb amide 6, which was used for Grignard reaction. The freshly prepared Grignard reagent 7 replaced the morpholine to result in ketone 8 with almost quantitative yield. Then an asymmetric Henry reaction was employed to set up chiral tertiary alcohol from ketone 8. After optimization of the reaction by screening chiral ligands (Table 1), ligand 9 was identified to provide optimal result, affording alcohol 10 with 80% ee in 75% yield. Upon reduction of the nitro group in 10 with hydrogen, the resulted amine 11 was used for chiral resolution by forming salt with (D)-tartaric acid 12. The enantiomer-enriched material salt 13 had an ee ratio of 99.4%. The salt 13, after being neutralized to release amine, was used for Suzuki reaction with boronic acid 14 to give intermediate 15, which was purified by forming crystallizable salt 16 with (D)-tartaric acid 12. With the hemi tartrate amine salt 16, an acid-catalyzed tetrazole formation reaction was applied to build the five-membered heterocyclic ring using sodium azide (NaN3) and triethyl orthoformate (HC(OEt)3) to deliver oteseconazole 1 in 85% yield. The impurity and ee ratio of 1 was further improved by forming benzensulfonate salt 18.