Benzaldehyde → HCID 178477573, compound

Participants

Reaction Steps

A solution of 17 g (78.23 mmol) of the acetate salt of 2-(4-amino-cyclohexyl)-1,1,1,3,3,3-hexafluoro-propan-2-ol (example 2.1) in 250 mL of ethanol was treated with 27.2 mL (196 mmol) of NEt3 and 8.75 mL (86.1 mmol) of benzaldehyde. The mixture was stirred overnight at RT and the solvents evaporated i.v. The brown oil obtained was dissolved in 120 mL of DMF and treated with 8.76 mL (58.7 mmol) of DBU and then dropwise with 9.85 mL (58.7 mmol) of TESCl. The mixture was stirred for 4 hrs at RT and distributed between a saturated aqueous solution of NH4Cl and Et2O. The crude material obtained after drying of the combined organic phases over Na2SO4 and evaporation of the solvent was dissolved in 250 mL of ethanol and treated portionwise with 2.2 g (58.7 mmol) of NaBH4 and stirred for 2 hrs at RT. Evaporation of the solvent, distribution between Et2O and an aqueous solution of NaOH, drying of the combined organic phases over Na2SO4 and chromatography on silica gel with heptane/EtOAc (gradient from 6:1 to 2:1) yielded 3.3 g (14%) of cis benzyl-[4-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-cyclohexyl]-amine and 4.7 g (20%) trans benzyl-[4-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-cyclohexyl]-amine as a yellow oil, MS: 470 (M+H)+.

Provenance & Evidence