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【结 构 式】

【分子编号】50410

【品名】4-[2-[4-((2S)-2-ethoxy-3-[[(1R)-2-hydroxy-1-phenylethyl]amino]-3-oxopropyl)phenoxy]ethyl]phenyl methanesulfonate

【CA登记号】

【 分 子 式 】C28H33NO7S

【 分 子 量 】527.63856

【元素组成】C 63.74% H 6.3% N 2.65% O 21.23% S 6.08%

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:(XI)

The reaction of 2-(4-hydroxyphenyl)ethyl alcohol (I) with Ms-Cl and TEA in dichloromethane gives the bis-methanesulfonate (II), which is condensed with 4-hydroxybenzaldehyde (III) by means of K2CO3 in acetonitrile to yield the substituted benzaldehyde (IV). The condensation of (IV) with phosphonium salt (V) by means of tetramethylguanidine (TMG) in chloroform affords the acrylic ester (VI), which is reduced with H2 over Pd/C in ethyl acetate to provide the propionic ester (VII). The hydrolysis of (VII) with LiOH in THF/water gives the propionic acid (VIII) as a racemic mixture, which is condensed with (R)-phenylglycinol (IX) by means of EDC, HOBt and DIEA in dichloromethane to yield the amide (X) as a diastereomeric mixture that is separated by crystallization and chromatography. The desired (S)-isomer (XI) is treated with H2SO4 in hot dioxane/water to furnish the target propionic acid.

1 McIntyre, J.A.; Castaner, J.; Bayes, M.; Tesaglitazar. Drugs Fut 2003, 28, 10, 959.
2 Andersson, K.; Boije, M.; Inghardt, T.; Lindstedt Alstermark, E.-L.; Gottfries, J.; Li, L. (AstraZeneca plc); New 3-aryl-2-aryl propionic acid derivs. and analogs. EP 1084101; EP 1084102; EP 1084103; WO 9962870; WO 9962871; WO 9962872 .
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) 47355 4-(2-hydroxyethyl)phenol 501-94-0 C8H10O2 详情 详情
(II) 50403 4-[2-[(methylsulfonyl)oxy]ethyl]phenyl methanesulfonate C10H14O6S2 详情 详情
(III) 13433 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde 123-08-0 C7H6O2 详情 详情
(IV) 50404 4-[2-(4-formylphenoxy)ethyl]phenyl methanesulfonate C16H16O5S 详情 详情
(V) 50405 (Ethoxy(ethoxycarbonyl)methyl)triphenylphosphonium chloride C24H26ClO3P 详情 详情
(VI) 50406 ethyl (E)-2-ethoxy-3-[4-([4-[(methylsulfonyl)oxy]phenethyl]oxy)phenyl]-2-propenoate C22H26O7S 详情 详情
(VII) 50407 ethyl 2-ethoxy-3-[4-([4-[(methylsulfonyl)oxy]phenethyl]oxy)phenyl]propanoate C22H28O7S 详情 详情
(VIII) 50408 2-ethoxy-3-[4-([4-[(methylsulfonyl)oxy]phenethyl]oxy)phenyl]propionic acid C20H24O7S 详情 详情
(IX) 14376 (2R)-2-amino-2-phenyl-1-ethanol; (R)-(-)-2-phenylglycinol; (R)-2-amino-2-phenyl-1-ethanol 56613-80-0 C8H11NO 详情 详情
(X) 50409 4-[2-[4-(2-ethoxy-3-[[(1R)-2-hydroxy-1-phenylethyl]amino]-3-oxopropyl)phenoxy]ethyl]phenyl methanesulfonate C28H33NO7S 详情 详情
(XI) 50410 4-[2-[4-((2S)-2-ethoxy-3-[[(1R)-2-hydroxy-1-phenylethyl]amino]-3-oxopropyl)phenoxy]ethyl]phenyl methanesulfonate C28H33NO7S 详情 详情
Extended Information