【结 构 式】 |
【分子编号】51608 【品名】ethyl 3-amino-4-oxopentanoate 【CA登记号】 |
【 分 子 式 】C7H13NO3 【 分 子 量 】159.18516 【元素组成】C 52.82% H 8.23% N 8.8% O 30.15% |
合成路线1
该中间体在本合成路线中的序号:(IV)Aspartic acid (I) was esterified with benzyl alcohol to afford the beta-benzyl ester (II). Dakin-West reaction of (II) with Ac2O and Et3N yielded the amido ketone (III). Acidic hydrolysis of (III), followed by re-esterification with EtOH, furnished amino ester (IV), which was acylated with acyl chloride (V), producing amide (VI). Cyclization between the amide and ketone groups of (VI) using Ac2O as the dehydrating reagent gave rise to the isoxazole (VII). The ester group of (VII) was then reduced to alcohol (VIII) with NaBH4 in the presence of AlCl3. Coupling of alcohol (VIII) with 4-nitrophenol (IX) to furnish ether (X) was effected either by Mitsunobu coupling or via previous conversion of (VIII) to the corresponding tosylate, followed by condensation with phenol (IX) under Williamson's ether synthesis conditions. Catalytic hydrogenation of the nitro group of (X) led to the aniline (XI). Finally, acylation of (XI) with trifluoromethanesulfonic anhydride provided the target sulfonamide.
【1】 Tomiyama, H.; et al.; Non-thiazolidinedione PPAR gamma- and alpha-dual agonists for the treatment of type II Diabetes mellitus. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 38. |
【2】 Kuroiwa, K.; Tomiyama, T.; Tomiyama, H.; Tomiyama, T. (Kotobuki Pharmaceutical Co., Ltd.); Ether or amide derivs., their preparation method and therapeutic agent for diabetes containing them. DE 10100772; JP 2001261662 . |
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) | 51614 | DL-2-Aminobutanedioic acid; DL-Aminosuccinic acid; DL-Asparaginic Acid; (+/-)-2-Aminosuccinic acid; DL-Aspartic acid; D,L-Aspartic acid | 617-45-8 | C4H7NO4 | 详情 | 详情 |
(II) | 51606 | Aspartic acid, 4-benzyl ester; L-Aspartic acid gamma-benzyl ester; beta-Benzyl L-aspartate | 2177-63-1 | C11H13NO4 | 详情 | 详情 |
(III) | 51607 | benzyl 3-(acetamido)-4-oxopentanoate | C14H17NO4 | 详情 | 详情 | |
(IV) | 51608 | ethyl 3-amino-4-oxopentanoate | C7H13NO3 | 详情 | 详情 | |
(V) | 36133 | 3,5-di(tert-butyl)-4-hydroxybenzoyl chloride | C15H21ClO2 | 详情 | 详情 | |
(VI) | 51609 | ethyl 3-[[3,5-di(tert-butyl)-4-hydroxybenzoyl]amino]-4-oxopentanoate | C22H33NO5 | 详情 | 详情 | |
(VII) | 51610 | ethyl 2-[2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-5-methyl-1,3-oxazol-4-yl]acetate | C22H31NO4 | 详情 | 详情 | |
(VIII) | 51611 | 2,6-di(tert-butyl)-4-[4-(2-hydroxyethyl)-5-methyl-1,3-oxazol-2-yl]phenol | C20H29NO3 | 详情 | 详情 | |
(IX) | 11236 | 4-Nitrophenol; p-Nitrophenol | 100-02-7 | C6H5NO3 | 详情 | 详情 |
(X) | 51612 | 2,6-di(tert-butyl)-4-[5-methyl-4-[2-(4-nitrophenoxy)ethyl]-1,3-oxazol-2-yl]phenol | C26H32N2O5 | 详情 | 详情 | |
(XI) | 51613 | 4-[4-[2-(4-aminophenoxy)ethyl]-5-methyl-1,3-oxazol-2-yl]-2,6-di(tert-butyl)phenol | C26H34N2O3 | 详情 | 详情 |