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【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information