2,2,2-Trifluoroethanol → HCID 66803241, compound

Participants

Reaction Steps

Di-tert-butyl azodicarboxylate (2.96 g, 12.83 mmol) was added to an ice cooled mixture of tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (2.00 g, 10.70 mmol), 2,2,2-trifluoroethanol (10.70 g, 106.95 mmol) and triphenylphosphine (3.37 g, 12.83 mmol) in THF (24 mL). The mixture was stirred at 70 C for 18 h. The mixture was concentrated under vacuum and the residue was purified by FCC, eluting with a gradient of EtOAc in heptane to afford tert-butyl (3S)-3-(2,2,2-trifluoroethoxy)pyrrolidine-1-carboxylate (0.393 g, 14%). This was dissolved in hydrogen chloride solution (4M in 1,4-dioxane, 3 mL, 12 mmol) and the mixture was stirred for 2 h. The mixture was concentrated to afford (3S)-3-(2,2,2-trifluoroethoxy)pyrrolidine hydrochloride (0.203 g, 68% yield). This was combined with 2-N-methyl-2-N-phenyl-6-[5-(trichloromethyl)-1,2,4-oxadiazol-3-yl]-1,3,5-triazine-2,4-diamine (prepared in an analogous manner to Intermediate 60, 0.1 g, 0.259 mmol) and potassium carbonate (0.13 g, 0.952 mmol) in DMF (2 mL) and the reaction mixture was stirred at room temperature for 16 h. The mixture was then concentrated and the residue dissolved in EtOAc. This was washed with saturated aq. sodium bicarbonate followed by brine, then dried over sodium sulfate and concentrated under vacuum. The residue was purified by preparative HPLC, Method D, to afford the title compound (0.006 g, 6%).

Provenance & Evidence