S1: Designing a Biocatalyst for the Synthesis of (S)-1-(2,6-Dichloro-3-fluorophenyl)ethanol

(S)-1-(2,6-Dichloro-3-fluorophenyl)ethanol (1) is a precursor used in the synthesis of several potent, orally bioavailable c-Met/ALK inhibitors currently in oncology clinical trials.  To enable the large-scale preparation of the drug substance, we required an efficient and scalable synthesis of 1 in optically pure form. In this report, we detail our efforts to produce 1 using a biotransformation-mediated process that affords the target molecule in high yield and excellent enantiomeric excess.