【结 构 式】 |
【分子编号】63048 【品名】sodium 1-ethanolate 【CA登记号】 |
【 分 子 式 】C2H5NaO 【 分 子 量 】68.050868 【元素组成】C 35.3% H 7.41% Na 33.78% O 23.51% |
合成路线1
该中间体在本合成路线中的序号:(XXIII)Reaction of chloroacetic acid (XXII) with sodium ethoxide (XXIII) in ethanol gives 2-ethoxyacetic acid ethyl ester (XXIV), which is condensed with 4-methoxybenz-aldehyde (XXV) by means of t-BuOK in THF to yield 2-ethoxy-3-(4-methoxyphenyl)-2-propenoic acid ethyl ester (XXVI). Hydrolysis of ester (XXVI) with NaOH in hot ethanol/water affords the propenoic acid derivative (XXVII), which is reduced with H2 over Pd/C in ethanol to provide racemic 2-ethoxy-3-(4-methoxyphenyl)propionic acid (XXVIII). Optical resolution of mixture (XXVIII) is performed by salt formation with 1(S)-(1-naphthyl)ethylamine (XXIX) followed by crystallization to give the diastereomeric salt (XXX), which is treated with NaOH, followed by acidification with HCl to yield 2(S)-ethoxy-3-(4-methoxyphenyl)propionic acid (XXXI). Demethylation of compound (XXXI) by reaction with NaOH and octanethiol in NMP affords 2(S)-ethoxy-3-(4-hydroxyphenyl)propionic acid (XXXII), which is esterified with ethanol/HCl to provide the corresponding ethyl ester (XXXIII). Condensation of ester (XXXIII) with the bismesylate (II) by means of either K2CO3 in 2-butanone or Na2CO3 in acetone provides 2(S)-ethoxy-3-[4-[2-[4-(methanesulfonyloxy)-phenyl]ethoxy]phenyl]propionic acid ethyl ester (XXI), which is finally hydrolyzed with NaOH or LiOH in acetone/water.
【1】 McIntyre, J.A.; Castaner, J.; Bayes, M.; Tesaglitazar. Drugs Fut 2003, 28, 10, 959. |
【2】 Ioannidis, P.; Ehrl, R.; MacKintosh, W. (AstraZeneca AB); Process for the preparation 3-aryl-2-hydroxypropionic acid deriv.. WO 0296865 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(II) | 50403 | 4-[2-[(methylsulfonyl)oxy]ethyl]phenyl methanesulfonate | C10H14O6S2 | 详情 | 详情 | |
(XX) | 50418 | ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate | C13H18O4 | 详情 | 详情 | |
(XXI) | 50419 | ethyl (2S)-2-ethoxy-3-[4-([4-[(methylsulfonyl)oxy]phenethyl]oxy)phenyl]propanoate | C22H28O7S | 详情 | 详情 | |
(XXII) | 11847 | 2-Chloroacetic acid; Chloroacetic Acid | 79-11-8 | C2H3ClO2 | 详情 | 详情 |
(XXIII) | 63048 | sodium 1-ethanolate | C2H5NaO | 详情 | 详情 | |
(XXIV) | 63049 | ethyl 2-ethoxyacetate | C6H12O3 | 详情 | 详情 | |
(XXV) | 27251 | 4-methoxybenzaldehyde; Anisicaldehyde; p-anisaldehyde | 123-11-5 | C8H8O2 | 详情 | 详情 |
(XXVI) | 63050 | ethyl (E)-2-ethoxy-3-(4-methoxyphenyl)-2-propenoate | C14H18O4 | 详情 | 详情 | |
(XXVII) | 63051 | (E)-2-ethoxy-3-(4-methoxyphenyl)-2-propenoic acid | C12H14O4 | 详情 | 详情 | |
(XXVIII) | 63052 | 2-ethoxy-3-(4-methoxyphenyl)propanoic acid | C12H16O4 | 详情 | 详情 | |
(XXIX) | 17443 | (1R)-1-(1-naphthyl)ethylamine; (1R)-1-(1-naphthyl)-1-ethanamine | 3886-70-2 | C12H13N | 详情 | 详情 |
(XXX) | 63053 | (1S)-1-(1-naphthyl)-1-ethanaminium (2S)-2-ethoxy-3-(4-methoxyphenyl)propanoate | C24H29NO4 | 详情 | 详情 | |
(XXXI) | 63054 | (2S)-2-ethoxy-3-(4-methoxyphenyl)propanoic acid | C12H16O4 | 详情 | 详情 | |
(XXXII) | 63055 | (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoic acid | C11H14O4 | 详情 | 详情 |