Triethylamine → (+/-)-Methyl {(2S*)-2-[4-(trifluoromethyl)phenyl]-1-[4,4,4-trifluoro-1-(3,3,3-trifluoropropyl)butyl]piperidin-4-yl}acetate

Participants

Reaction Conditions

Reaction Steps

Intermediate 2 (301 mg, 1 mmol), 1,1,1,7,7,7-hexafluoroheptan-4-one (500 mg, 2 mmol) and triethylamine (0.8 mL, 6 mmol) were dissolved in CH2Cl2 (4 mL) and the mixture was cooled to −78° C. TiCl4 (2 mL, 1M in CH2Cl2) was added dropwise to give a dark orange mixture. This mixture was allowed to warm to 0° C. for 5 min then re-cooled to −78° C. NaCNBH3 (376 mg, 6 mmol) in methanol (2 mL) was added and the mixture was warmed to room temperature. The mixture was diluted with water and ethyl acetate and was filtered through celite to remove titanium salts. The organic extracts were pooled, washed with brine, dried and evaporated. The residue was purified on silica using 20-50% CH2Cl2 in iso-hexane as eluant to give the product as a crystalline solid (85 mg, 20%) upon evaporation.

Provenance & Evidence