反应详情

To a stirred solution of spiro[cyclopentane-1,3′-indol]-2′(1′H)-one (600 mg, 3.2 mmol, Howard, Harry R. et al., J. Med. Chem., 1996, 39, 143) and triethylamine (972 mg, 9.6 mmol) in CH2Cl2 (20 mL) was added 4-nitrochloroformate (677 mg, 3.4 mmol) at room temperature, and stirred at ambient temperature for 3 h. Then, a solution of tert-butyl 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylate (1.0 g, 3.2 mmol, step 5 of Example 1) in CH2Cl2 (5 mL) was added at room temperature, and stirred for 18 h. Then, sat. NaHCO3 aq. (20 mL) was added, extracted with CH2Cl2 (30 mL×3), dried over MgSO4, filtered and concentrated gave yellow brown oil. The residue was chromatographed on a column of aminopropyl-silica gel eluting with hexane/ethyl acetate (11:1) to give 1.3 g (75%) of the title compound as clear yellow oil.

1. stirringstirred for 18 h
2. extractionextracted with CH2Cl2 (30 mL×3)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customgave yellow brown oil
7. customThe residue was chromatographed on a column of aminopropyl-silica gel eluting with hexane/ethyl acetate (11:1)