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【结 构 式】

【分子编号】50414

【品名】3-[4-(benzyloxy)phenyl]-2-ethoxy-N-[(1R)-2-hydroxy-1-phenylethyl]propanamide

【CA登记号】

【 分 子 式 】C26H29NO4

【 分 子 量 】419.5206

【元素组成】C 74.44% H 6.97% N 3.34% O 15.25%

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:(XVI)

The condensation of 4-(benzyloxy)benzaldehyde (XII) with phosphonium salt (V) by means of TMG as before gives the acrylic ester (XIII), which is hydrogenated with H2 over Rh/C in methanol to yield the propionic ester (XIV). The hydrolysis of (XIV) with LiOH in dioxane/water affords the corresponding acid (XV) as a racemic mixture, which is condensed with (R)-phenylglycinol (IX) by means of EDC, HOBt and DIEA in dichloromethane to provide the amide (XVI) as a diastereomeric mixture that is separated by crystallization and chromatography. The desired (S)-isomer (XVII) is treated with H2SO4 in hot dioxane/water to furnish the chiral propionic acid (XVIII), which is esterified with EtOH and HCl to give the ethyl propionate (XIX). The hydrogenolysis of the benzyl ether group of (XIX) with H2 over Pd/C in ethyl acetate yields the phenolic derivative (XX), which is condensed with the bis-methanesulfonate by means of K2CO3 in acetonitrile to afford the adduct (XXI). Finally, the ester group of (XXI) is hydrolyzed with LiOH in THF/water to provide 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
(II) 50403 4-[2-[(methylsulfonyl)oxy]ethyl]phenyl methanesulfonate C10H14O6S2 详情 详情
(V) 50405 (Ethoxy(ethoxycarbonyl)methyl)triphenylphosphonium chloride C24H26ClO3P 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
(XII) 29179 4-(Benzyloxy)benzaldehyde 4397-53-9 C14H12O2 详情 详情
(XIII) 50411 ethyl (E)-3-[4-(benzyloxy)phenyl]-2-ethoxy-2-propenoate C20H22O4 详情 详情
(XIV) 50412 ethyl 3-[4-(benzyloxy)phenyl]-2-ethoxypropanoate C20H24O4 详情 详情
(XV) 50413 3-[4-(benzyloxy)phenyl]-2-ethoxypropionic acid C18H20O4 详情 详情
(XVI) 50414 3-[4-(benzyloxy)phenyl]-2-ethoxy-N-[(1R)-2-hydroxy-1-phenylethyl]propanamide C26H29NO4 详情 详情
(XVII) 50415 (2S)-3-[4-(benzyloxy)phenyl]-2-ethoxy-N-[(1R)-2-hydroxy-1-phenylethyl]propanamide C26H29NO4 详情 详情
(XVIII) 40516 methyl (1R,5R)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate C10H15NO2 详情 详情
(XIX) 50417 ethyl (2S)-3-[4-(benzyloxy)phenyl]-2-ethoxypropanoate C20H24O4 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
Extended Information