Potassium Carbonate → 1-(4-Methoxyphenyl)-2-pyrrolidinone
반응식
[NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].I[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1.C(=O)([O-])[O-].[K+].[K+]>[Cu]>[CH3:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([N:1]2[CH2:5][CH2:4][CH2:3][C:2]2=[O:6])=[CH:9][CH:10]=1참가 물질
5
실험 절차
In step a of the overall synthesis, 2-pyrrolidinone and 4-iodoanisole are heated in the presence of copper powder and potassium carbonate to give the N-(4-methoxyphenyl)pyrrolidin-2-one, which in step b is treated with ethylmagnesium bromide Grignard reagent to give an aliphatic ketone after ring opening of the pyrrolidinone. This ketone is isolated and then undergoes ring closure to form the 3-hydroxy-1,2,5,6-tetrahydropyridin-2-one intermediate in steps c and d using ethyl oxalyl chloride and sodium hydroxide in step c and sodium ethoxide and ethanol in step d. The corresponding 3-methoxy intermediate is obtained in step e by treatment with 3-methyl-p-tolyltriazine, after which in step f the 4,5,6,7-tetrahydro-7-oxo-1H-pyrazolo[3,4-c]pyridine intermediate is obtained by ring closure using cyclopentyl hydrazine hydrochloride. The 4-methoxyphenyl N-protecting group is removed in step g by treatment with cerium (IV) ammonium nitrate to give the lactam intermediate, after which in step h the lactam intermediate is converted to the corresponding thiolactam intermediate by treatment with phosphorus pentasulfide. The tricyclic final product is prepared in steps i′, j and k by treatment with anhydrous hydrazine in step i, followed by treatment with 2-thiophene carbonyl chloride in step j and refluxing in step k.