methyl (2S)-2-hydroxy-3-methoxy-3,3-diphenylpropanoate -Drug Synthesis Database

【结构式】

【分子编号】38710

【品名】methyl (2S)-2-hydroxy-3-methoxy-3,3-diphenylpropanoate

【CA登记号】

【分子式】C₁₇H₁₈O₄

【分子量】286.32752

【元素组成】C 71.31% H 6.34% O 22.35%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

The esterification of 2(S)-hydroxy-3-methoxy-3,3-diphenylpropionic acid (I) with NaOMe and dimethyl sulfate gives the methyl ester (II), which is submitted to and acid (TsOH) catalyzed transetherification with 2-(3,4-dimethoxyphenyl)ethanol (III) to yield 3-[2-(3,4-dimethoxyphenyl)ethoxy-2(S)-hydroxy-3,3-diphenylpropionic acid methyl ester (IV). The hydrolysis of (IV) with KOH in methanol affords the corresponding free acid (V), which is finally condensed with 4,6-dimethyl-2-(methylsulfonyl)pyrimidine (VI) by means of lithium amide in DMF.

参考文献中间体

合成目标

【1】 Jansen, R.; Hillen, H.; Kettschau, G.; Unger, L.; Hergenröder, S.; Kling, A.; Raschack, M.; Klinge, D.; Riechers, H.; Amberg, W.; Discovery and synthesis of (S)-3-[2-(3,4-dimethoxyphenyl)ethoxy]-2-(4,6-dimethylpyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 302872), a novel orally active mixed ETA/ETB receptor antagonist. J Med Chem 1999, 42, 16, 3026.

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)	21154	(2S)-2-hydroxy-3-methoxy-3,3-diphenylpropionic acid		C₁₆H₁₆O₄	详情	详情
(II)	38710	methyl (2S)-2-hydroxy-3-methoxy-3,3-diphenylpropanoate		C₁₇H₁₈O₄	详情	详情
(III)	38711	2-(3,4-dimethoxyphenyl)-1-ethanol	7417-21-2	C₁₀H₁₄O₃	详情	详情
(IV)	38712	methyl (2S)-3-[(3,4-dimethoxyphenethyl)oxy]-2-hydroxy-3,3-diphenylpropanoate		C₂₆H₂₈O₆	详情	详情
(V)	38713	(2S)-3-[(3,4-dimethoxyphenethyl)oxy]-2-hydroxy-3,3-diphenylpropionic acid		C₂₅H₂₆O₆	详情	详情
(VI)	38714	4,6-dimethyl-2-(methylsulfonyl)pyrimidine; 4,6-dimethyl-2-pyrimidinyl methyl sulfone		C₇H₁₀N₂O₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The condensation of benzophenone (I) with methyl 2-chloroacetate (II) by means of NaOMe in THF gives 3,3-diphenyloxirane-2-carboxylic acid methyl ester (III), which by treatment with BF3/Et2O and methanol, followed by optical resolution, yielded the pure enantiomer 2(S)-hydroxy-3-methoxy-3,3-diphenylpropionic acid methyl ester (IV). The condensation of (IV) with 4,6-dimethyl-2-(methylsulfonyl)pyrimidine (V) by means of K2CO3 in DMF affords 2-(4,6-dimethylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropionic acid methyl ester (VI), which is finally hydrolyzed with KOH in hot dioxane to afford the target propionic acid as a racemic mixture.

参考文献中间体

合成目标

【1】 Riechers, H.; Albrecht, H.-P.; Amberg, W.; et al.; Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists. J Med Chem 1996, 39, 11, 2123.

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)	18732	benzophenone	119-61-9	C₁₃H₁₀O	详情	详情
(II)	10257	methyl 2-chloroacetate; methyl chloroacetate	96-34-4	C₃H₅ClO₂	详情	详情
(III)	21148	methyl 3,3-diphenyl-2-oxiranecarboxylate		C₁₆H₁₄O₃	详情	详情
(IV)	38710	methyl (2S)-2-hydroxy-3-methoxy-3,3-diphenylpropanoate		C₁₇H₁₈O₄	详情	详情
(V)	38714	4,6-dimethyl-2-(methylsulfonyl)pyrimidine; 4,6-dimethyl-2-pyrimidinyl methyl sulfone		C₇H₁₀N₂O₂S	详情	详情
(VI)	56710	methyl (2S)-2-[(4,6-dimethyl-2-pyrimidinyl)oxy]-3-methoxy-3,3-diphenylpropanoate		C₂₃H₂₄N₂O₄	详情	详情

Extended Information