Sodium Iodide → HCID 86638555, compound

Participants

Reaction Steps

To a stirred solution of (R)-tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (231 mg, 1.07 mmol), 2-(4-(bromomethyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (400 mg, 1.19 mmol) and sodium iodide (18 mg, 0.12 mmol) in acetonitrile (10 mL) was added potassium carbonate (655 mg, 4.75 mmol). The reaction mixture was stirred at room temperature for 3 days, before being diluted with dichloromethane (10 mL), filtered through cotton wool and concentrated under reduced pressure. The residue was purified by flash column chromatography (eluting with dichloromethane to 10% methanol in dichloromethane) to afford the intermediate (R)-tert-butyl 4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)-3-(hydroxymethyl)piperazine-1-carboxylate (250 mg, 0.53 mmol). To a stirred solution of (R)-tert-butyl 4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)-3-(hydroxymethyl)piperazine-1-carboxylate (220 mg, 0.466 mmol) in dichloromethane (3 mL), was added trifluoroacetic acid (3 mL, 38.3 mmol). The reaction mixture was stirred at room temperature for 5 hours before being purified directly by SCX chromatography, eluting with 2N ammonia in methanol solution to afford the title compound (165 mg). MS (ESI) m/z 373.3 [M+H]+

Provenance & Evidence