【结 构 式】 |
【分子编号】10119 【品名】3,5-Dibromo-4-(2-piperidinoethoxy)benzoic acid 【CA登记号】 |
【 分 子 式 】C14H17Br2NO3 【 分 子 量 】407.10192 【元素组成】C 41.31% H 4.21% Br 39.26% N 3.44% O 11.79% |
合成路线1
该中间体在本合成路线中的序号:(V)The synthesis of radiolabeled raloxifene has been reported: The esterification of 3,5-dibromo-4-hydroxybenzoic acid (I) with methanol/HCl gives the corresponding methyl ester (II), which is condensed with 1-(2-chloroethyl)piperidine (III) by means of K2CO3 in DMF yielding 3,5-dibromo-4-[2-(1-piperidyl)ethoxy]benzoic acid methyl ester (IV). The hydrolysis of (IV) with NaOH in methanol affords the corresponding free acid (V), which by treatment of SOCl2 in toluene is converted to the acyl chloride (VI). The Friedel-Crafts condensation of (VI) with 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene (VII) by means of AlCl3 in dichloromethane gives [3,5-dibromo-4-[2-(1-piperidinyl)ethoxy]phenyl]-[6-methoxy-2-(4-methoxy phenyl)benzo[b]thien-3-yl]methanone (VIII), which is demethylated with AlCl3 and ethylmercaptane to dibromoraloxifene (IX). Finally, this compound is submitted to hydrogenolysis with tritium over Pd/C in methanol.
【1】 Dodge, J.A.; Stocksdale, M.G.; Jones, C.D.; A chemical probe for the estrogen receptor: Synthesis of the H-3 isotopomer of raloxifene. J Label Compd Radiopharm 1995, 36, 1, 43. |
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) | 10115 | 3,5-Dibromo-4-hydroxybenzoic acid | 3337-62-0 | C7H4Br2O3 | 详情 | 详情 |
(II) | 10116 | methyl 3,5-dibromo-4-hydroxybenzoate | 41727-47-3 | C8H6Br2O3 | 详情 | 详情 |
(III) | 10117 | 1-(2-Chloroethyl)piperidine; N-(2-Chloroethyl)piperidine | 1932-03-2 | C7H14ClN | 详情 | 详情 |
(IV) | 10118 | methyl 3,5-dibromo-4-(2-piperidinoethoxy)benzoate | C15H19Br2NO3 | 详情 | 详情 | |
(V) | 10119 | 3,5-Dibromo-4-(2-piperidinoethoxy)benzoic acid | C14H17Br2NO3 | 详情 | 详情 | |
(VI) | 10120 | 3,5-Dibromo-4-(2-piperidinoethoxy)benzoyl chloride | C14H16Br2ClNO2 | 详情 | 详情 | |
(VII) | 10121 | 4-(6-Methoxy-1-benzothiophen-2-yl)phenyl methyl ether; 6-Methoxy-2-(4-methoxyphenyl)-1-benzothiophene | 63675-74-1 | C16H14O2S | 详情 | 详情 |
(VIII) | 10122 | [3,5-Dibromo-4-[2-(1-piperidinyl)ethoxy]phenyl][6-methoxy-2-(4-methoxyphenyl)-1-benzothiophen-3-yl]methanone | C30H29Br2NO4S | 详情 | 详情 | |
(IX) | 10123 | [3,5-Dibromo-4-[2-(1-piperidinyl)ethoxy]phenyl][6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]methanone | C28H25Br2NO4S | 详情 | 详情 |