Ammonium Chloride → 1,2-Propanediol, 2-methyl-3-[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl]phenoxy]-, (2R)-

Participants

Reaction Conditions

Reaction Steps

(R)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diol (87.96 g, 336.9 mmol, optical purity of 92.2% ee), 4-[4-(trifluoromethoxy)phenoxy]piperidine (80 g, 306.2 mmol), tris(dibenzylideneacetone)dipalladium (0) (Pd2dba3, 701 mg, 0.77 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (780 mg, 1.84 mmol), sodium tert-butoxide (33.85 g, 352.2 mmol), and toluene (240 ml) were mixed, followed by stirring under an argon atmosphere at 70° C. for 6 hours. After cooling, an ammonium chloride aqueous solution was added to the reaction mixture, followed by extraction with toluene. Thereafter, the organic layer was distilled off under reduced pressure, obtaining a crude product of (R)-2-methyl-3-(4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenoxy)propane-1,2-diol.

Provenance & Evidence