Hydrochloric Acid → HCID 178461662, compound

Participants

Reaction Conditions

Reaction Steps

Hydrogen chloride gas was bubbled into a solution of ((R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-{(1S,2S)-1-[4-chloro-5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propylcarbamoyl}-methyl)-carbamic acid tert-butyl ester (440 mg, 0.55 mmol) in dioxane for 15 minutes at room temperature and the resulting mixture was allowed to stir under an atmosphere of nitrogen for 3 hours. The reaction was concentrated in vacuo and the residue was dissolved in tetrahydrofuran (15 mL) containing triethylamine (609 μL, 4.37 mmol). Chlorotrimethylsilane (416 μL, 3.28 mmol) was added via syringe at room temperature and the resulting mixture was allowed to stir under an atmosphere of nitrogen for one hour. The reaction was poured into water (10 mL) and extracted with ethyl acetate (2×25 mL). The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product, dissolved in tetrahydrofuran (5 mL) containing N,N-diisopropylethylamine was added via an addition funnel to diphosgene (46 μL, 0.38 mmol) in 1:1 v/v toluene/tetrahydrofuran (5 mL) at −78° C. under an atmosphere of nitrogen with stirring. The reaction was allowed to warm to 10° C. then quenched with ice/water (5 mL) and stirred for 2 minutes. The mixture was acidified with 1.0 N aqueous hydrochloric acid solution (10 mL), stirred for 5 minutes then extracted with ethyl acetate (2×25 mL). The organic extracts were combined, washed with water (2×10 mL), brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted with 50 to 80% v/v ethyl acetate/hexanes to give (R)-3-{(1S,2S)-1-[4-chloro-5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-5-[4-(2-hydroxy-ethoxy)-phenyl]-imidazolidine-2,4-dione (229 mg, 62%). HR-MS: calcd for C29H25ClFlN4O4 [M+H+] 675.0666. Found 675.0660.

Provenance & Evidence