【结 构 式】 |
【分子编号】56202 【品名】4-[(8S,11R,13S,14S,17S)-17-methoxy-17-(methoxymethyl)-13-methyl-3-oxo-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl]benzaldehyde 【CA登记号】 |
【 分 子 式 】C28H34O4 【 分 子 量 】434.57556 【元素组成】C 77.39% H 7.89% O 14.73% |
合成路线1
该中间体在本合成路线中的序号:(IX)After protection of 4-bromobenzaldehyde (I) with triethyl orthoformate in MeOH, the resultant bromo ketal (II) was converted to the corresponding Grignard reagent (III) with magnesium in THF. Conjugate addition of (III) to the steroid epoxide (IV) in the presence of CuCl gave rise to the 11-beta-aryl steroid (V). Introduction of a 17-spiro oxirane moiety into ketone (V) to yield (VI) was accomplished by reaction with the sulfur ylide generated from trimethylsulfonium iodide and potassium tert-butoxide. Subsequent epoxide opening in (VI) with NaOMe gave rise to the methoxy alcohol (VII), which was further alkylated with iodomethane under Williamson's ether synthesis conditions to provide the dimethoxy derivative (VIII). Acid hydrolysis of both ketal groups of (VIII) with concomitant alcohol dehydration led to the dienone (IX). The aldehyde function of (IX) was finally converted to the target oxime by treatment with hydroxylamine hydrochloride in pyridine.
【1】 Schubert, G.; Kaufmann, G.; Sobeck, L.; Oettel, M.; Elger, W.; Kurischko, A. (Jenapharm GmbH); 11-Benzaldoximeestradiene-derivates, a process for their preparation and pharmaceutical compsns. containing them. CA 2130516; DE 4322283; EP 0648778 . |
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) | 22231 | 4-Bromobenzaldehyde | 1122-91-4 | C7H5BrO | 详情 | 详情 |
(II) | 23438 | (4-bromophenyl)(methoxy)methyl methyl ether; 1-bromo-4-(dimethoxymethyl)benzene | C9H11BrO2 | 详情 | 详情 | |
(III) | 30851 | bromo[4-(dimethoxymethyl)phenyl]magnesium | C9H11BrMgO2 | 详情 | 详情 | |
(IV) | 56197 | C20H28O4 | 详情 | 详情 | ||
(V) | 56198 | (5R,8S,11R,13S,14S)-11-[4-(dimethoxymethyl)phenyl]-5-hydroxy-3,3-dimethoxy-13-methyl-1,2,3,4,5,6,7,8,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C29H40O6 | 详情 | 详情 | |
(VI) | 56199 | C30H42O6 | 详情 | 详情 | ||
(VII) | 56200 | (8S,11R,13S,14S,17S)-11-[4-(dimethoxymethyl)phenyl]-3,3-dimethoxy-17-(methoxymethyl)-13-methyl-1,2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-5H-cyclopenta[a]phenanthrene-5,17-diol | C31H46O7 | 详情 | 详情 | |
(VIII) | 56201 | (8S,11R,13S,14S,17S)-11-[4-(dimethoxymethyl)phenyl]-3,3,17-trimethoxy-17-(methoxymethyl)-13-methyl-1,2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-5H-cyclopenta[a]phenanthren-5-ol | C32H48O7 | 详情 | 详情 | |
(IX) | 56202 | 4-[(8S,11R,13S,14S,17S)-17-methoxy-17-(methoxymethyl)-13-methyl-3-oxo-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl]benzaldehyde | C28H34O4 | 详情 | 详情 |