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【结 构 式】 
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【分子编号】62431 【品名】ethyl (E)-3-(4-methoxyphenyl)-2-propenoate 【CA登记号】 |
【 分 子 式 】C12H14O3 【 分 子 量 】206.24136 【元素组成】C 69.89% H 6.84% O 23.27% |
合成路线1
该中间体在本合成路线中的序号：(I)Electrophilic bromination of ethyl p-methoxycinnamate (I) by means of N-bromosuccinimide in moist acetone gave rise to the racemic erythro bromohydrin (II), which was esterified with butyric anhydride to produce the racemic bromoester (III). Kinetic resolution of (III) employing Candida cylindracea lipase caused the enantioselective hydrolysis of the (S,S)-enantiomer, yielding the chiral bromohydrin (V). Cyclization of (V) in the presence of NaOMe furnished epoxide (VI). The target thiazepinone (VIII) was then obtained by condensation between the glycidic ester (VI) and 2-aminobenzenethiol (VII)
| 【1】 McCague, R.; Wang, S.; Taylor, S.J.C. (Celltech Group plc); Chiral arylpropionates and their use. WO 9413828 . |
| 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) | 25047 | butyric anhydride | 106-31-0 | C8H14O3 | 详情 | 详情 |
| (I) | 62431 | ethyl (E)-3-(4-methoxyphenyl)-2-propenoate | C12H14O3 | 详情 | 详情 | |
| (II) | 62432 | ethyl (2S,3S)-2-bromo-3-hydroxy-3-(4-methoxyphenyl)propanoate | C12H15BrO4 | 详情 | 详情 | |
| (III) | 62433 | (1S,2S)-2-bromo-3-ethoxy-1-(4-methoxyphenyl)-3-oxopropyl butyrate | C16H21BrO5 | 详情 | 详情 | |
| (IV) | 62434 | (1R,2R)-2-bromo-3-ethoxy-1-(4-methoxyphenyl)-3-oxopropyl butyrate | C16H21BrO5 | 详情 | 详情 | |
| (V) | 62432 | ethyl (2S,3S)-2-bromo-3-hydroxy-3-(4-methoxyphenyl)propanoate | C12H15BrO4 | 详情 | 详情 | |
| (VI) | 62435 | ethyl (2R,3S)-3-(4-methoxyphenyl)-2-oxiranecarboxylate | C12H14O4 | 详情 | 详情 | |
| (VII) | 25182 | 2-aminobenzenethiol | 137-07-5 | C6H7NS | 详情 | 详情 |
| (VIII) | 62436 | (2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | C16H15NO3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)A different method for the preparation of glycidic ester (VI) consists in the asymmetric epoxidation of ethyl 4-methoxycinnamate (I) with oxone(R) in the presence of chiral macrocyclic ketones, such as the binaphthyl ketone (IX)
| 【1】 Seki, M.; Furutani, T.; Imashiro, R.; Kuroda, T.; Yamanaka, T.; Harada, N.; Arawaka, H.; Kusama, M.; Hashiyama, T.; A novel synthesis of a key intermediate for diltiazem. Tetrahedron Lett 2001, 42, 46, 8201. |
| 【2】 Ozaki, Y.; Arakawa, H.; Harada, N.; Hashiyama, T.; Kuroda, T.; Seki, M.; Kusama, M. (Tanabe Seiyaku Co., Ltd.); Process for preparing optically active phenyloxirane cpds.. WO 9856762 . |
合成路线3
该中间体在本合成路线中的序号：(I)A different strategy to reach the amino ester precursor (XXIX) was developed starting from the chiral diol (XXX), readily accessible by asymmetric dihydroxylation of cinnamate (I). Reaction of diol (XXX) with SOCl2 produced the cyclic sulfite (XXXI) (12,14). Optionally, diol (XXX) was condensed with phosgene to produce the cyclic carbonate (XXXII) (12). Opening of either sulfite (XXXI) or carbonate (XXXII) with 2-aminothiophenol (VIII) proceeded with retention of the configuration, leading to the desired intermediate aminoacid (XXIX)
| 【1】 Lohray, B.B.; Jayachandran, B.; Bhushan, V.; Nandanan, E.; Ravindranathan, T.; Anchimeric assisted unprecedented SN(i)-type cleavage of cyclic sulfite: Application in the synthesis of the calcium channel blocker diltiazem. J Org Chem 1995, 60, 18, 5983. |
| 【2】 Hulshof, L.A.; Kuilman, T.; Process for preparing 1,5-benzothiazepin derivs.. EP 0450705 . |
| 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) | 62431 | ethyl (E)-3-(4-methoxyphenyl)-2-propenoate | C12H14O3 | 详情 | 详情 | |
| (VIII) | 25182 | 2-aminobenzenethiol | 137-07-5 | C6H7NS | 详情 | 详情 |
| (XXIX) | 62448 | (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid | C16H17NO4S | 详情 | 详情 | |
| (XXX) | 62449 | ethyl (2R,3S)-2,3-dihydroxy-3-(4-methoxyphenyl)propanoate | C12H16O5 | 详情 | 详情 | |
| (XXXI) | 62450 | ethyl (4R,5S)-5-(4-methoxyphenyl)-2-oxo-1,3,2lambda~4~-dioxathiolane-4-carboxylate | C12H14O6S | 详情 | 详情 | |
| (XXXII) | 62451 | ethyl (4R,5S)-5-(4-methoxyphenyl)-2-oxo-1,3-dioxolane-4-carboxylate | C13H14O6 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)The precursor cis-cinnamate (XXXIX) can be obtained by several synthetic routes. Bromination of ethyl trans-4-methoxycinnamate (I) afforded the dibromo ester (XXXVI), which underwent dehydrohalogenation and hydrolysis to the arylpropiolic acid (XXXVII) upon treatment with ethanolic KOH. Acid (XXXVII) was converted to the corresponding isopropyl ester (XXXVIII) by DCC-mediated coupling with isopropanol. Semihydrogenation of (XXXVIII) in the presence of Lindlar catalyst led to the required cis cinnamate (XXXIX). Alternatively, anisaldehyde (X) was converted to the gem-dibromostyrene (XL) by condensation with CBr4 in the presence of PPh3. Reaction of (XL) with BuLi, followed by addition of isopropyl chloroformate to the resultant lithium acetylide, furnished the arylpropiolate (XXXVIII). In another method to obtain the cis-cinnamate (XXXIX), trans-4-methoxycinnamic acid (XLI) was converted to the isopropyl ester (XLII), which was then photochemically isomerized to the desired cis-cinnamate (XXXIX)
| 【1】 Jacobsen, E.N.; Deng, L.; Furukawa, Y.; Martinez, L.E.; Enantioselective catalytic epoxidation of cinnamate esters. Tetrahedron 1994, 50, 15, 4323. |
| 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) | 62431 | ethyl (E)-3-(4-methoxyphenyl)-2-propenoate | C12H14O3 | 详情 | 详情 | |
| (X) | 27251 | 4-methoxybenzaldehyde; Anisicaldehyde; p-anisaldehyde | 123-11-5 | C8H8O2 | 详情 | 详情 |
| (XXXVI) | 62454 | ethyl 2,3-dibromo-3-(4-methoxyphenyl)propanoate | C12H14Br2O3 | 详情 | 详情 | |
| (XXXVII) | 62455 | 3-(4-methoxyphenyl)-2-propynoic acid | C10H8O3 | 详情 | 详情 | |
| (XXXVIII) | 62457 | isopropyl 3-(4-methoxyphenyl)-2-propynoate | C13H14O3 | 详情 | 详情 | |
| (XXXIX) | 62458 | isopropyl (Z)-3-(4-methoxyphenyl)-2-propenoate | C13H16O3 | 详情 | 详情 | |
| (XL) | 62456 | 1-(2,2-dibromovinyl)-4-methoxybenzene; 4-(2,2-dibromovinyl)phenyl methyl ether | C9H8Br2O | 详情 | 详情 | |
| (XLI) | 42108 | (E)-3-(4-methoxyphenyl)-2-propenoic acid | 830-09-1 | C10H10O3 | 详情 | 详情 |
| (XLII) | 63416 | isopropyl (E)-3-(4-methoxyphenyl)-2-propenoate | C13H16O3 | 详情 | 详情 |