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【结 构 式】 
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【分子编号】25553 【品名】ethyl (6R,8S)-8-methyl-9-oxo-5,6,8,9-tetrahydrothiepino[4,5-f][1,3]benzodioxole-6-carboxylate 【CA登记号】 |
【 分 子 式 】C15H16O5S 【 分 子 量 】308.35504 【元素组成】C 58.43% H 5.23% O 25.94% S 10.4% |
合成路线1
该中间体在本合成路线中的序号：(V)Condensation of halo ester (I) with 2-mercaptopropionic acid (II) provided thioether (III). After conversion of the carboxylic acid group of (III) into acid chloride (IV), Friedel-Crafts cyclization yielded the racemic trans benzothiepinone (V). Subsequent ester hydrolysis gave carboxylic acid (VI). The required (2R,4S) enantiomer (IX) was then isolated by condensation with methyl (R)-mandelate (VII), followed by recrystallization of the diastereoisomeric ester (VIII) from ethyl acetate-hexane, and further hydrolysis with HCl in AcOH. Finally, coupling of (IX) with diethyl 4-aminobenzylphosphonate (X) by means of EDC and HOBt furnished the title compound.
| 【1】 Oda, T.; et al.; Synthesis of novel 2-benzothiopyran and 3-benzothiepin derivatives and their stimulatory effect on bone formation. Symp Med Chem 1998, Abst 2-P-31. |
| 【2】 Sohda, T.; Taketomi, S.; Oda, T. (Takeda Chemical Industries, Ltd.); Optically active benzothiepine deriv., its preparation and use. CA 2166152; EP 0719782; JP 1996231569; JP 1997183784 . |
| 【3】 Hoshino, T.; Muranishi, H.; Taketomi, S.; Iwasa, S. (Takeda Chemical Industries, Ltd.); Osteogenetic promoting pharmaceutical compsn.. JP 1997263545; WO 9639134 . |
| 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) | 25550 | ethyl 3-(1,3-benzodioxol-5-yl)-2-bromopropanoate | C12H13BrO4 | 详情 | 详情 | |
| (II) | 24361 | 2-sulfanylpropionic acid; 2-mercaptopropionic acid | 57965-30-7 | C3H6O2S | 详情 | 详情 |
| (III) | 25552 | 2-[[1-(1,3-benzodioxol-5-ylmethyl)-2-ethoxy-2-oxoethyl]sulfanyl]propionic acid | C15H18O6S | 详情 | 详情 | |
| (IV) | 25551 | ethyl 3-(1,3-benzodioxol-5-yl)-2-[(2-chloro-1-methyl-2-oxoethyl)sulfanyl]propanoate | C15H17ClO5S | 详情 | 详情 | |
| (V) | 25553 | ethyl (6R,8S)-8-methyl-9-oxo-5,6,8,9-tetrahydrothiepino[4,5-f][1,3]benzodioxole-6-carboxylate | C15H16O5S | 详情 | 详情 | |
| (VI) | 24367 | 8(S)-Methyl-9-oxo-5,6,8,9-tetrahydro-1,3-dioxolo[4,5-h][3]benzothiepine-6(R)-carboxylic acid | C13H12O5S | 详情 | 详情 | |
| (VII) | 25554 | methyl (2R)-2-hydroxy-2-phenylethanoate | 20698-91-3 | C9H10O3 | 详情 | 详情 |
| (VIII) | 24366 | 8(S)-Methyl-9-oxo-5,6,8,9-tetrahydro-1,3-dioxolo[4,5-h][3]benzothiepine-6(R)-carboxylic acid 1(R)-(methoxycarbonyl)-1-benzyl ester | C22H20O7S | 详情 | 详情 | |
| (IX) | 24367 | 8(S)-Methyl-9-oxo-5,6,8,9-tetrahydro-1,3-dioxolo[4,5-h][3]benzothiepine-6(R)-carboxylic acid | C13H12O5S | 详情 | 详情 | |
| (X) | 24368 | 4-Aminobenzylphosphonic acid diethyl ester | 20074-79-7 | C11H18NO3P | 详情 | 详情 |