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【结 构 式】 
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【分子编号】30542 【品名】2-[1-(2-hydroxy-2-oxoethyl)cyclohexyl]acetic acid 【CA登记号】4355-11-7 |
【 分 子 式 】C10H16O4 【 分 子 量 】200.23464 【元素组成】C 59.98% H 8.05% O 31.96% |
合成路线1
该中间体在本合成路线中的序号：(III)Reaction of cyclohexenone (I) with ethyl cyanoacetate (A) in the presence of ammonia affords the Guareschi salt (II), which is hydrolyzed and decarboxylated to give 1,1-cyclohexanediacetic acid (III). The anhydride (IV) can be treated either with methanol to yield the halfester (V), or with hydroxylamine to afford the N-hydroxyimide (VII). The halfester (V) is subjected to a Curtius type rearrangement to give the isocyanate (VI), which is hydrolyzed to the amino acid hydrochloride (Xl).
| 【1】 Satzinger, G.; Hartenstein, J. (Pfizer Inc.); Cyclic sulphonyloxyimides. DE 2611690; ES 457050; FR 2344540; GB 1575709; JP 52113977; US 4152326 . |
| 【2】 Satzinger, G.; Hartenstein, J.; Herrmann, M.; Heldt, W. (Pfizer Inc.); Cyclic aminoacids. DE 2460891; ES 443723; FR 2294697; GB 1465229; JP 51088940; US 4024175 . |
| 【3】 Castaner, J.; Serradell, M.N.; Gabapentin. Drugs Fut 1984, 9, 6, 418. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 11877 | Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate | 105-56-6 | C5H7NO2 | 详情 | 详情 |
| (I) | 11059 | Cyclohexanone | 108-94-1 | C6H10O | 详情 | 详情 |
| (II) | 30541 | 3',5'-Dicyano-2',4'-dioxospiro[cyclohexane-1,4'-piperidide] ammonium salt | C12H16N4O2 | 详情 | 详情 | |
| (III) | 30542 | 2-[1-(2-hydroxy-2-oxoethyl)cyclohexyl]acetic acid | 4355-11-7 | C10H16O4 | 详情 | 详情 |
| (IV) | 30543 | 3-oxaspiro[5.5]undecane-2,4-dione | C10H14O3 | 详情 | 详情 | |
| (V) | 30544 | 2-[1-(2-methoxy-2-oxoethyl)cyclohexyl]acetic acid | C11H18O4 | 详情 | 详情 | |
| (VI) | 30545 | methyl 2-[1-(isocyanatomethyl)cyclohexyl]acetate | C11H17NO3 | 详情 | 详情 | |
| (XI) | 30546 | 2-[1-(aminomethyl)cyclohexyl]acetic acid | 60142-96-3 | C9H17NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)The same product can be obtained from reaction of cyclohexenone (I) with ethyl cyanoacetate (A) in the presence of ammonia affords the Guareschi salt (II), which is hydrolyzed and decarboxylated to give 1,1-cyclohexanediacetic acid (III). The anhydride (IV) can be treated with the N-hydroxyimide (VII) via a Lossen type rearrangement by conversion of (VII) to N-benzenesulfonyloxylmide (VIII) and subsequent reaction with triethylamine in methanol followed by hydrolysis of the urethanester (IX). The free amino acid is finally obtained from the hydrochloride (X) via anion exchange.
| 【1】 Satzinger, G.; Hartenstein, J. (Pfizer Inc.); Cyclic sulphonyloxyimides. DE 2611690; ES 457050; FR 2344540; GB 1575709; JP 52113977; US 4152326 . |
| 【2】 Satzinger, G.; Hartenstein, J.; Herrmann, M.; Heldt, W. (Pfizer Inc.); Cyclic aminoacids. DE 2460891; ES 443723; FR 2294697; GB 1465229; JP 51088940; US 4024175 . |
| 【3】 Castaner, J.; Serradell, M.N.; Gabapentin. Drugs Fut 1984, 9, 6, 418. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 11877 | Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate | 105-56-6 | C5H7NO2 | 详情 | 详情 |
| (I) | 11059 | Cyclohexanone | 108-94-1 | C6H10O | 详情 | 详情 |
| (II) | 30541 | 3',5'-Dicyano-2',4'-dioxospiro[cyclohexane-1,4'-piperidide] ammonium salt | C12H16N4O2 | 详情 | 详情 | |
| (III) | 30542 | 2-[1-(2-hydroxy-2-oxoethyl)cyclohexyl]acetic acid | 4355-11-7 | C10H16O4 | 详情 | 详情 |
| (IV) | 30543 | 3-oxaspiro[5.5]undecane-2,4-dione | C10H14O3 | 详情 | 详情 | |
| (VII) | 30547 | 3-hydroxy-3-azaspiro[5.5]undecane-2,4-dione | C10H15NO3 | 详情 | 详情 | |
| (VIII) | 30548 | 3-[(phenylsulfonyl)oxy]-3-azaspiro[5.5]undecane-2,4-dione | C16H19NO5S | 详情 | 详情 | |
| (IX) | 30549 | methyl 2-(1-[[(methoxycarbonyl)amino]methyl]cyclohexyl)acetate | C12H21NO4 | 详情 | 详情 | |
| (X) | 30546 | 2-[1-(aminomethyl)cyclohexyl]acetic acid | 60142-96-3 | C9H17NO2 | 详情 | 详情 |