Cerium(III) Chloride-Mediated Stereoselective Reduction of a 4-Substituted Cyclohexanone Using NaBH4

Several additives were screened for the stereoselective reduction of a 4-substituted cyclohexanone en route to linrodostat mesylate. It was found that the addition of sub-stoichiometric cerium(III) chloride in conjunction with sodium borohydride provided the desired trans-cyclohexanol (arising out of axial delivery of the hydride onto the carbonyl) in >16:1 selectivity and excellent conversion. The reaction was initially scaled up to 3.5 kg scale and eventually to >100 kg scale.