Cl.C([O:6][C:7]([N:9]1[CH2:14][CH:13]([CH3:15])[N:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[C:11](=[O:24])[CH2:10]1)=O)(C)(C)C.[CH:25](N(CC)C(C)C)(C)C.C(OC(=O)C)(=O)C>C(OCC)(=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:7]([N:9]1[CH2:14][CH:13]([CH3:15])[N:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[C:11](=[O:24])[CH2:10]1)(=[O:6])[CH3:25]A steady stream of anhydrous HCl gas was bubbled through a cold (0° C.) solution of 4-[(tert-butoxy)carbonyl]-1-(4-fluorobenzyl)-6-methylpiperazin-2-one (0.62 g, 1.9 mmol) in ethyl acetate (20 mL) for 5 minutes. The resultant mixture was capped and stirred at the same temperature for 1 h. The product mixture was concentrated under vacuum. The residue was treated with a mixture of N,N-diisopropylethylamine (1.00 mL, 5.8 mmol), DMAP (5 mg), and acetic anhydride (0.22 mL, 2.3 mmol) in methylene chloride (10 mL). The resultant mixture was concentrated and the residue was subjected to column chromatography on silica gel eluting with a mixture of 10% methanol in ethyl acetate. Collection and concentration of appropriate fractions provided the title piperazinone.
読み込み中…
