反应详情

A 250 mL round-bottomed flask was charged with tert-butyl 4-(2-bromo-4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-1-piperazinecarboxylate (3.70 g, 8.16 mmol), 25 mL of EtOAc, and 8 mL of 4M HCl in dioxane (32 mmol). After heating at reflux for 30 min, the mixture was cooled and concentrated. The resulting viscous oil was dissolved in 30 mL of CH2Cl2 and triethylamine (3.98 mL, 28.6 mmol). At 0° C., 2-thiophenesulfonyl chloride (1.49 g, 8.16 mmol, Sigma-Aldrich, St. Louis, Mo.) was added at 0° C. After 15 min, the mixture was concentrated then re-dissolved in 5 mL of CH2Cl2, filtered, and purified via column chromatography (120 g of silica, 0 to 50% EtOAc in hexanes) to give 2-(3-bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1-trifluoro-2-propanol (2.75 g) as a white solid.

1. temperatureAfter heating
2. temperatureat reflux for 30 min
3. temperaturethe mixture was cooled
4. concentrationconcentrated
5. dissolutionThe resulting viscous oil was dissolved in 30 mL of CH2Cl2
6. concentrationthe mixture was concentrated
7. dissolutionthen re-dissolved in 5 mL of CH2Cl2
8. filtrationfiltered
9. custompurified via column chromatography (120 g of silica, 0 to 50% EtOAc in hexanes)