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【结 构 式】 
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【分子编号】48327 【品名】N-[3,3-diphenyldihydro-2(3H)-furanylidene]-N-methylmethanaminium bromide 【CA登记号】 |
【 分 子 式 】C18H20BrNO 【 分 子 量 】346.26694 【元素组成】C 62.44% H 5.82% Br 23.08% N 4.05% O 4.62% |
合成路线1
该中间体在本合成路线中的序号：(V)Treatment of 2-oxo-3,3-diphenyl-tetrahydrofuran (I) with HBr(g) yields bromo derivative (II), which is then converted into butyryl chloride derivative (III) by means of thionyl chloride in refluxing chloroform. Reaction of derivative (III) with dimethylamine (IV) in toluene affords dimethyl (tetrahydro-3,3-diphenyl-2-furylidene)ammonium bromide (V), which is then condensed with 4-(4-chlorophenyl)-4-piperidinol (VI) by means of Na2CO3 and KI in refluxing 4-methyl-2-pentanone to provide N,N-dimethyl butyramide derivative (VII). Finally, the target product is obtained by N-oxidation of the piperidine ring in (VII) by heating with H2O2 in MeOH/methylbenzene or in 4-methyl-2-pentanone.
| 【1】 Cooymans, L.P.; Wals, L. (Janssen Pharmaceutica NV); Novel alpha,alpha-diaryl-4-aryl-4-hydroxy-1-piperidinebutanamide, N-oxides. EP 0219898; JP 1987087569; US 4824853; US 4898873 . |
| 【2】 Niemegeers, C.J.E.J.; Janssen, P.A.J.; Stokbroekx, R.A.; Vandenberk, J. (Janssen Pharmaceutica NV); 2,2-Diaryl-4-(4'-aryl-4'-hydroxy-piperidino)-butyramides. US 3714159 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 48324 | alpha,alpha-Diphenyl-gamma-butyrolactone; 4-Methoxychalcone; (4-Methoxybenzylidene)acetophenone; Dihydro-3,3-diphenyl-2(3H)-furanone; 4-Hydroxy-2,2-diphenylbutyric acid gamma-lactone; alpha,alpha-Diphenylbutyrolactone | 959-33-1 | C16H14O2 | 详情 | 详情 |
| (II) | 48325 | 4-bromo-2,2-diphenylbutyric acid | C16H15BrO2 | 详情 | 详情 | |
| (III) | 48326 | 4-bromo-2,2-diphenylbutanoyl chloride | C16H14BrClO | 详情 | 详情 | |
| (IV) | 19443 | N-methylmethanamine; N,N-dimethylamine | 124-40-3 | C2H7N | 详情 | 详情 |
| (V) | 48327 | N-[3,3-diphenyldihydro-2(3H)-furanylidene]-N-methylmethanaminium bromide | C18H20BrNO | 详情 | 详情 | |
| (VI) | 35870 | 4-(4-chlorophenyl)-4-piperidinol; 4-(4-Chlorophenyl)-4-hydroxypiperidine | 39512-49-7 | C11H14ClNO | 详情 | 详情 |
| (VII) | 48328 | 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-N,N-dimethyl-2,2-diphenylbutanamide | C29H33ClN2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The target disubstituted piperazine was generated by the ring opening of dimethyl (tetrahydro-3,3-diphenyl-2-furylidene)ammonium bromide (I), equivalent to the open-chain bromobutyramide, with N-(2-methoxyphenyl)piperazine (II) in hot DMF. Subsequent treatment with HCl in CHCl3-Et2O provided the corresponding hydrochloride salt.
| 【1】 Komoto, T.; et al.; New mu-opioid receptor agonists with piperazine moiety. Chem Pharm Bull 2001, 49, 10, 1314. |