反应详情

To a solution of (1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentanamine dihydrochloride (140 mg, 0.31 mmol), 3-methyltetrahydro-4H-pyran-4-one (70 mg, 0.61 mmol) and triethylamine (0.21 mL, 1.5 mmol) in methylene chloride (10 mL) was added sodium triacetoxyborohydride (190 mg, 0.92 mmol). After being stirred overnight, the reaction mixture was diluted with EtOAc and washed with saturated Na2CO3. The aqueous layer was extracted with EtOAc three times. The combined organic layers were dried (MgSO4), concentrated and purified by flash chromatography on silica gel (EtOAc to 1% Et3N/EtOAc to 5% Et3N/EtOAc) to give 101 mg of product. The product was further separated by chiral HPLC to give isomer 1 and isomer 2. MS calculated for C25H37F3N4O2 (M+1) 483; found 483.2.

1. washwashed with saturated Na2CO3
2. extractionThe aqueous layer was extracted with EtOAc three times
3. dry with materialThe combined organic layers were dried (MgSO4)
4. concentrationconcentrated
5. custompurified by flash chromatography on silica gel (EtOAc to 1% Et3N/EtOAc to 5% Et3N/EtOAc)