反应详情

温度

25 °C

A solution of 297 mg (1.68 mmol) 2-(isopropyl-methyl-amino)-4-methyl-pentanoic acid, 0.88 mL (5 mmol) N,N-diisopropylethylamine, and 636 mg (1.68 mmol) O-Benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)uronium hexafluorophosphate in 4 mL dry DMF was stirred at 3° for 60 minutes, at which time 500 mg (1.68 mmol) 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride was added and the reaction stirred an additional 10 minutes at 3°, then warmed to 25° C. for 40 minutes at which time it was diluted with 20 mL diethyl ether and washed with 20 mL saturated aqueous sodium bicarbonate solution and twice with 20 mL brine, dried over anhydrous sodium sulfate and concentrated at reduced pressure. The residue thus obtained was further purified by silica gel chromatography using 60% ethyl acetate in hexanes as eluant, followed by conversion to the hydrochloride salt by treating with excess diethyl ether which had been saturated with hydrogen chloride gas to give 648 mg (83%) of titled compound: mp 155-156° C. APCI-MS m/z 431.4 (MH+).

1. additionwas added
2. washwashed with 20 mL saturated aqueous sodium bicarbonate solution and twice with 20 mL brine
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated at reduced pressure
5. customThe residue thus obtained
6. customwas further purified by silica gel chromatography
7. additionby treating with excess diethyl ether which