2-(4-Bromophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol → HCID 86670448, compound

Participants

Reaction Conditions

Reaction Steps

A 20 mL vial was charged with tert-butyl (3R)-3-((benzyloxy)methyl)-1-piperazinecarboxylate (1.19 g, 3.88 mmol), 2-(4-bromophenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1.39 g, 4.31 mmol, Bioorg. Med. Chem. Lett. 2002, 12, 3009), RuPhos Palladacycle (0.047 g, 0.039 mmol, Strem Chemical Inc, Newburyport, Mass.), NaOtBu (0.938 g, 9.76 mmol, Sigma-Aldrich, St. Louis, Mo.) and toluene (12 mL). The mixture was degassed by bubbling Ar through the solution for 10 min. The vial was sealed and the mixture was heated at 100° C. for 3 h. Water (100 mL) was added and the aqueous phase was extracted with EtOAc (2×60 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (100 g of silica, 0-30% EtOAc in hexanes) to afford tert-butyl (3R)-3-((benzyloxy)methyl)-4-(4-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-1-piperazinecarboxylate (1.78 g) as an off-white foam.

Provenance & Evidence