C([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[C:15]2=[O:27])[CH2:10][CH2:9]1)C1C=CC=CC=1.CO.Cl.[H][H]>[Pd].O>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19]([N:16]2[CH2:17][CH2:18][N:14]([CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[C:15]2=[O:27])=[CH:20][CH:21]=1A solution of 33 g of 1-benzyl-4-piperidone and 29 g of 1-(4-methoxy-phenyl)-ethylenediamine in 310 ml of methanol, with the addition of 1 g of a 5% platinum on charcoal catalyst, is hydrogenated at room temperature and under normal pressure until 1 molar equivalent of hydrogen has been taken up. The catalyst is thereafter removed by filtration and the filtrate concentrated. The residue is treated with toluene to yield the 1-benzyl-4-[2-4-methoxy-anilino)-ethylamino]-piperidine as a yellowish oil, which is used without purification. With vigorous stirring, 87 g of phosgene gas are introduced at 5° to 10° C. in the course of 21/2 hours into a mixture of 63 g of 1-benzyl-4-[2-(4-methoxy-anilino)-ethylamino]-piperidin in 570 ml of toluene and 285 ml of 2 3 N aqueous potassium hydroxide solution. Stirring is continued for a further 2 hours at room temperature and then 252 ml of a 6 N aqueous potassium hydroxide solution are added dropwise in the course of 15 minutes, when a slightly exothermic reaction occurs. The reaction mixture is stirred for a further 20 hours at room temperature. Thereafter the organic phase is separated and the alkaline aqueous phase is extracted with two 100 ml portions of toluene. The organic extracts are dried over sodium sulphate and concentrated under reduced pressure. The residue is treated with toluene and recrystallised from isopropanol to yield 1-(1-benzyl-4-piperidyl)-3-(4-methoxy-phenyl)-imidazolidin-2-one with a melting point of 144°-147° C. A mixture of 44 g of 1-(1-benzyl-4-piperidyl)-3-(4-methoxyphenyl)-imidazolidin-2-one, 320 ml of methanol, 130 ml of water and 12 g of a conc. aqueous solution of hydrochloric acid, with the addition of 10 g of a palladium on charcoal catalyst, is hydrogenated at 30° to 40° C. and under reduced pressure until 1 molar equivalent of hydrogen has been taken up. Thereafter the catalyst is removed by filtration and the filtrate is concentrated under reduced pressure. The residue is treated with toluene and recrystallised from a mixture of isopropyl alcohol and diethyl ether to yield the 1-(4-methoxyphenyl)-3-(4-piperidyl)-2-imidazolidinone with a melting point of 140° C.
読み込み中…
