反应详情

A solution of 4-(4-hydroxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (1.5 g, 5.4 mmol) in dry tetrahydrofuran (5 mL) is added to suspension of sodium hydride (431 mg, 60% in oil, 10.8 mmol) in dry tetrahydrofuran (35 mL). After 15 minutes reaction time, a solution of 1-bromomethyl-4-trifluoromethyl-benzene (1.9 g, 8.1 mmol) in tetrahydrofuran (5 mL) is added. The reaction is stirred for 16 hours at room temperature, is filtered and concentrated under vacuum. The residue obtained is diluted in ethyl acetate (40 mL) and the organic layer is washed with water (3×20 mL), is dried over magnesium sulfate, filtered and concentrated under vacuum. The residue obtained is dissolved in a 1 to 1 mixture of dichloromethane and trifluoroacetic acid (30 mL), and stirred for 30 minutes. The mixture is then concentrated under vacuum, and co-evaporated in dichloromethane (30 mL). The resulting residue is diluted in diethylether (5 mL) and a molar solution of hydrochloric acid in diethylether is added (10 mL). The precipitate formed is filtered, washed with diethylether (10 mL) and dried under vacuum. The desired product is isolated as hydrochloride as a colorless solid in the presence of traces of solvent.

1. customAfter 15 minutes reaction time
2. filtrationis filtered
3. concentrationconcentrated under vacuum
4. customThe residue obtained
5. washthe organic layer is washed with water (3×20 mL)
6. dry with materialis dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. customThe residue obtained
10. stirringstirred for 30 minutes
11. concentrationThe mixture is then concentrated under vacuum
12. additionThe resulting residue is diluted in diethylether (5 mL)
13. additiona molar solution of hydrochloric acid in diethylether is added (10 mL)
14. customThe precipitate formed
15. filtrationis filtered
16. washwashed with diethylether (10 mL)
17. customdried under vacuum