【结 构 式】 |
【分子编号】35479 【品名】 【CA登记号】 |
【 分 子 式 】C11H14O3 【 分 子 量 】194.23036 【元素组成】C 68.02% H 7.27% O 24.71% |
合成路线1
该中间体在本合成路线中的序号:(I)The cyclopropanation of (-)-2,3-(cyclohexylidenedioxy)-4-cyclopentenone (I) with (ethoxycarbonylmethyl)dimethylsulfonium bromide (II) by means of DBU in chloroform gives the bicyclo[3.1.0]hexane derivative (II), which is treated with chloroform and LiHMDS in THF yielding the trichloromethyl derivative (IV). The reaction of (IV) with sodium azide, DBU and 18-crown-6 in methanol affords the azido-dicarboxylate derivative (V), which is hydrogenated with H2 over Pd/C in ethyl acetate to give the amino-dicarboxylic ester (VI). The acylation of (VI) with acetyl chloride and TEA in dichloromethane yields the corresponding acetamide (VII), which is treated with TFA to afford the bicyclic diol (VIII). The esterification of (VIII) with triethyl orthoformate provides the cyclic orthoester (IX), which is decomposed thermically at 170-90 C giving the unsaturated bicyclic compound (X). The hydrogenation of (X) with H2 over Pd/C in ethyl acetate affords the saturated compound (XI), which is finally deacetylated and hydrolyzed by a treatment with refluxing 1H aqueous HCl.
【1】 Dominguez Fernandez, C.; Ezquerra Carrera, J.; Baker, S.R.; Monn, J.A. (Eli Lilly and Company; Lilly SA); Bicyclohexane derivs.. WO 0004010 . |
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) | 35479 | C11H14O3 | 详情 | 详情 | ||
(II) | 11947 | (2-Ethoxy-2-oxoethyl)(dimethyl)sulfonium bromide | 5187-82-6 | C6H13BrO2S | 详情 | 详情 |
(III) | 35480 | C15H20O5 | 详情 | 详情 | ||
(IV) | 35481 | C16H21Cl3O5 | 详情 | 详情 | ||
(V) | 35482 | C16H21N3O6 | 详情 | 详情 | ||
(VI) | 35483 | C16H23NO6 | 详情 | 详情 | ||
(VII) | 35484 | C18H25NO7 | 详情 | 详情 | ||
(VIII) | 35485 | dimethyl (1S,2R,3S,4R,5R,6R)-2-(acetamido)-3,4-dihydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate | C12H17NO7 | 详情 | 详情 | |
(IX) | 35486 | dimethyl (3aR,3bR,4R,4aS,5R,5aS)-5-(acetamido)-2-ethoxyhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-4,5-dicarboxylate | C15H21NO8 | 详情 | 详情 | |
(X) | 35487 | dimethyl (1S,2S,5R,6S)-2-(acetamido)bicyclo[3.1.0]hex-3-ene-2,6-dicarboxylate | C12H15NO5 | 详情 | 详情 | |
(XI) | 35488 | dimethyl (1S,2S,5R,6S)-2-(acetamido)bicyclo[3.1.0]hexane-2,6-dicarboxylate | C12H17NO5 | 详情 | 详情 |