【结 构 式】 |
【分子编号】35994 【品名】3-(3-hydroxyphenyl)-1-propyl-2,6-piperidinedione 【CA登记号】 |
【 分 子 式 】C14H17NO3 【 分 子 量 】247.29392 【元素组成】C 68% H 6.93% N 5.66% O 19.41% |
合成路线1
该中间体在本合成路线中的序号:(XV)The condensation of (3-methoxyphenyl)acetonitrile (VIII) with 3-bromopropyltetrahydropyranyl ether (IX) by means of lithium diisopropylamide in THF gives 2-(3-methoxyphenyl)-5-tetrahydropyranyloxypentanonitrile (X), which is oxidized with chromic anhydride-H2SO4 yielding 4-cyano-3-(3-methoxyphenyl)butyric acid (XI). The hydrolysis of (XI) with KOH in ethanol-water affords 2-(3-methoxyphenyl)glutaric acid (XII), which is anhydrized with refluxing acetic anhydride giving 2-(3-methoxyphenyl)glutaric anhydride (XIII). The reaction of (XIII) with propylamine (C) in refluxing benzene yields 2-(3-methoxyphenyl)-N-propylglutarimide (XIV), which is demethylated with BBr3 in methylene chloride to 2-(3-hydroxyphenyl)-N-propylglutarimide (XV). The benzylation of (XV) with benzyl bromide and K2CO3 in DMF affords 2-(3-benzyloxyphenyl)-N-propylglutarimide (XVI), which is reduced with LiAlH4 in THF giving 3-(3-benzyloxyphenyl)-N-propylpiperidine (XVII). Finally, this compound is debenzylated by hydrogenolysis with H2 over Pd/C in AcOH.
【1】 Brands, F.T.L.; Loozen, H.J.J.; An efficient synthesis of 3-arylpiperidines. J R Neth Chem Soc 1981, 100, 9, 333-336. |
【2】 Serradell, M.N.; Nohria, V.; Castaner, J.; Blancafort, P.; 3-PPP. Drugs Fut 1983, 8, 1, 27. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 | |
(VIII) | 24061 | 3-methoxyphenylacetonitrile; 2-(3-methoxyphenyl)acetonitrile | 19924-43-7 | C9H9NO | 详情 | 详情 |
(IX) | 29460 | 2-(4-bromobutoxy)tetrahydro-2H-pyran; 4-bromobutyl tetrahydro-2H-pyran-2-yl ether | C9H17BrO2 | 详情 | 详情 | |
(X) | 35989 | 2-(3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)hexanenitrile | C18H25NO3 | 详情 | 详情 | |
(XI) | 35990 | 4-cyano-4-(3-methoxyphenyl)butyric acid | C12H13NO3 | 详情 | 详情 | |
(XII) | 35991 | 2-(3-methoxyphenyl)pentanedioic acid | C12H14O5 | 详情 | 详情 | |
(XIII) | 35992 | 3-(3-methoxyphenyl)dihydro-2H-pyran-2,6(3H)-dione | C12H12O4 | 详情 | 详情 | |
(XIV) | 35993 | 3-(3-methoxyphenyl)-1-propyl-2,6-piperidinedione | C15H19NO3 | 详情 | 详情 | |
(XV) | 35994 | 3-(3-hydroxyphenyl)-1-propyl-2,6-piperidinedione | C14H17NO3 | 详情 | 详情 | |
(XVI) | 35995 | 3-[3-(benzyloxy)phenyl]-1-propyl-2,6-piperidinedione | C21H23NO3 | 详情 | 详情 | |
(XVII) | 35996 | benzyl 3-(1-propyl-3-piperidinyl)phenyl ether; 3-[3-(benzyloxy)phenyl]-1-propylpiperidine | C21H27NO | 详情 | 详情 | |
(C) | 23923 | 1-propanamine | 107-10-8 | C3H9N | 详情 | 详情 |