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【结 构 式】 
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【分子编号】31287 【品名】5-(4-chlorophenyl)-1-azaspiro[5.5]undecan-5-ol 【CA登记号】 |
【 分 子 式 】C16H22ClNO 【 分 子 量 】279.80952 【元素组成】C 68.68% H 7.92% Cl 12.67% N 5.01% O 5.72% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Fischer esterification of 1-aminocyclohexanecarboxylic acid (I) provided the ethyl ester (II), which was alkylated with ethyl 4-bromobutyrate (III) in the presence of K2CO3 at 100 C to give aminodiester (IV). Dieckmann cyclization of (IV) using NaOEt afforded the azaspiro ketoester (V), which was decarboxylated under acidic conditions to yield ketone (VI). Addition of 4-chlorophenylmagnesium bromide (VII) to (VI) produced the tertiary acohol (VIII). This was dehydrated with concentrated H2SO4 to give the corresponding olefin as the sulfate salt, which was further treated with NaOH and then with HCl to furnish the corresponding hydrochloride.
| 【1】 Harris, P.J.; Kerrigan, F. (The Boots Company plc); Aza spiro alkanes derivs. as therapeutic agents. EP 0667860; JP 1996502985; US 5610161; WO 9411346 . |
| 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) | 31282 | 1-aminocyclohexanecarboxylic acid | 2756-85-6 | C7H13NO2 | 详情 | 详情 |
| (II) | 31283 | ethyl 1-aminocyclohexanecarboxylate | C9H17NO2 | 详情 | 详情 | |
| (III) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
| (IV) | 31284 | ethyl 1-[(4-ethoxy-4-oxobutyl)amino]cyclohexanecarboxylate | C15H27NO4 | 详情 | 详情 | |
| (V) | 31285 | ethyl 5-oxo-1-azaspiro[5.5]undecane-4-carboxylate | C13H21NO3 | 详情 | 详情 | |
| (VI) | 31286 | 1-azaspiro[5.5]undecan-5-one | C10H17NO | 详情 | 详情 | |
| (VII) | 25127 | bromo(4-chlorophenyl)magnesium | 873-77-8 | C6H4BrClMg | 详情 | 详情 |
| (VIII) | 31287 | 5-(4-chlorophenyl)-1-azaspiro[5.5]undecan-5-ol | C16H22ClNO | 详情 | 详情 |