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【结 构 式】 
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【分子编号】37477 【品名】(1S,5R,13R,16R,17R)-10-methoxy-4-methyl-16-vinyl-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one 【CA登记号】 |
【 分 子 式 】C20H23NO3 【 分 子 量 】325.40756 【元素组成】C 73.82% H 7.12% N 4.3% O 14.75% |
合成路线1
该中间体在本合成路线中的序号：(V)This compound can be obtained in two related ways: 1) The reaction of codeinon (I) with ethyllithium and CuI in ether gives 4,5alpha-epoxy-8beta-ethyl-3-methoxy-17-methylmorphinan-6-one (II), which by treatment with cyanogen bromide and K2CO3 in CHCl3 is converted into 17-cyano-4,5alpha-epoxy-8beta-ethyl-3-methoxymorphinan-6-one (III). Elimination of the cyano group of (III) by treatment with refluxing aqueous 2N HCl yields 4,5alpha-epoxy-8beta-ethyl-3-methoxymorphinan-6-one (IV), which is finally alkylated with cyclopropylmethyl bromide (C) and NaHCO3 in DMF at 100 C. 2) The reaction of codeinon (I) with vinyl bromide (A), tert-butyllithium and CuI in ether gives 4,5alpha-epoxy-3-methoxy-17-methyl-8beta-vinylmorphinanone (V), which is reduced with H2, Pd/C in ethanol to yield (II).
| 【1】 Kotick, M.P.; DE 2900918 . |
| 【2】 Hillier, K.; Castaner, J.; Codorphone Hydrochloride. Drugs Fut 1981, 6, 12, 766. |
| 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) | 28790 | 1-bromoethylene | 593-60-2 | C2H3Br | 详情 | 详情 |
| (B) | 37473 | Ethyl lithium; Ethyllithium | 811-49-4 | C2H5Li | 详情 | 详情 |
| (I) | 37472 | (1S,5R,13R,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10,15-tetraen-14-one | C18H19NO3 | 详情 | 详情 | |
| (II) | 37474 | (1S,5R,13R,16S,17R)-16-ethyl-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one | C20H25NO3 | 详情 | 详情 | |
| (III) | 37475 | (1S,5R,13R,16S,17R)-4-cyano-16-ethyl-10-methoxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one | C20H22N2O3 | 详情 | 详情 | |
| (IV) | 37476 | (1S,5R,13R,16S,17R)-16-ethyl-10-methoxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one | C19H23NO3 | 详情 | 详情 | |
| (V) | 37477 | (1S,5R,13R,16R,17R)-10-methoxy-4-methyl-16-vinyl-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one | C20H23NO3 | 详情 | 详情 | |
| (C) | 22277 | Cyclopropyl bromide; 1-(Bromomethyl)cyclopropane | 7051-34-5 | C4H7Br | 详情 | 详情 |