To a solution of 2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehyde (180 g, 377 mmol) in anhydrous dichloromethane (1.5 L) at 0° C. is sequentially added sodium borohydride (7.2 g, 188.5 mmol) and anhydrous methanol (0.5 L) and the contents are allowed to reach room temperature while stirring 30 min. LC/MS analysis of the reaction mixture reveals completion. Volatiles are removed under reduced pressure and the residue obtained is partitioned between dichloromethane (2 L) and water (300 mL). The layers are separated and the organic layer is sequentially washed with 1 N aqueous solution of sodium hydroxide (300 mL), water (3×300 mL), brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue is purified on silica gel using 50-55% ethyl acetate in hexane containing 1% triethylamine to afford [2-[4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methanol as a solid (167 g, 92% yield). MS (m/z): 481 (M+1).
