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【结 构 式】

【分子编号】10874

【品名】3-acetyl-2,5,6-trimethylphenyl acetate

【CA登记号】

【 分 子 式 】C13H16O3

【 分 子 量 】220.26824

【元素组成】C 70.89% H 7.32% O 21.79%

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:(I)

A new synthesis of [14C]-labeled CS-045 has been reported: The condensation of 5-acetoxy-2-hydroxy-3,4,6-trimethylacetophenone (I) with phenoxyacetone (II) by means of morpholine and p-toluenesulfonic acid in refluxing benzene gives 6-acetoxy-2,5,7,8-tetramethyl-2-(phenoxymethyl)-3,4-dihydro-2H-benzo[b]pyran-4-one (III), which is reduced with NaBH4 in methanol to the corresponding carbinol (IV). The dehydration of (IV) by means of p-toluenesulfonic acid in refluxing benzene affords 2-acetoxy-2,5,7,8-tetramethyl-2-(phenoxymethyl)-2H-benzo[b]pyran (V), which is hydrogenated with H2 over Pd/C in methanol to give the corresponding 3,4-dihydro derivative (VI). The hydrolysis of (VI) with NaOH in methanol yields the corresponding phenol (VII), which is chloromethylated with paraformaldehyde and dry HCl in dioxane to afford 2-[4-(chloromethyl)phenoxymethyl]-2,5,7,8-tetramethyl-3,4-dihydro-2H-benzo[b]pyran-6-ol (VIII). The protection of (VIII) with chloromethyl methyl ether by means of potassium tert-butoxide in THF gives the corresponding 6-(methoxymethoxy) derivative (IX), which is condensed with [5-14C]-thiazolidine-2,4-dione (X) by means of butyllithium in THF-HMPT to yield 5-[4-[6-(methoxymethoxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-benzo[b]pyran-2-ylmethoxy]benzyl]-[5-14C]-thiazolidine-2,4-dione (XI). Finally, this compound is deprotected with concentrated HCl in ethylene glycol monomethyl ether at 130 C.

1 Prous, J.; Castaner, J.; CS-045. Drugs Fut 1989, 14, 9, 846.
2 Aizawa, Y.; Yoshioka, T.; Fujita, T.; Kawai, K.; Kanai, T.; Studies on hindered phenols. III. Synthesis of (±)-5-[4-(6-hydroxy-2,5,7,8 -tetramethyl-chroman-2-yl-methoxy)benzyl]-5-14C-thiazolidine-2,4-dione (14C-labelled CS-045). J Label Compd Radiopharm 1990, 28, 8, 911.
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) 10874 3-acetyl-2,5,6-trimethylphenyl acetate C13H16O3 详情 详情
(II) 10875 1-Phenoxyacetone; 1-Phenoxy-2-propanone 621-87-4 C9H10O2 详情 详情
(III) 10876 2,5,7,8-tetramethyl-4-oxo-2-(phenoxymethyl)-3,4-dihydro-2H-chromen-6-yl acetate C22H24O5 详情 详情
(IV) 10877 4-hydroxy-2,5,7,8-tetramethyl-2-(phenoxymethyl)-3,4-dihydro-2H-chromen-6-yl acetate C22H26O5 详情 详情
(V) 10878 2,5,7,8-tetramethyl-2-(phenoxymethyl)-2H-chromen-6-yl acetate C22H24O4 详情 详情
(VI) 10879 2,5,7,8-tetramethyl-2-(phenoxymethyl)-3,4-dihydro-2H-chromen-6-yl acetate C22H26O4 详情 详情
(VII) 10880 2,5,7,8-Tetramethyl-2-(phenoxymethyl)-6-chromanol C20H24O3 详情 详情
(VIII) 10881 2-[[4-(Chloromethyl)phenoxy]methyl]-2,5,7,8-tetramethyl-6-chromanol C21H25ClO3 详情 详情
(IX) 10882 2-[[4-(Chloromethyl)phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-6-yl methoxymethyl ether; 2-[[4-(Chloromethyl)phenoxy]methyl]-6-(methoxymethoxy)-2,5,7,8-tetramethylchromane C23H29ClO4 详情 详情
(X) 10883 1,3-Thiazolane-2,4-dione; 2,4-Thiazolidinedione 2295-31-0 C3H3NO2S 详情 详情
(X) 44682 1,3-thiazolidine-2,4-dione C3H3NO2S 详情 详情
(XI) 10884 5-(4-[[6-(Methoxymethoxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methoxy]benzyl)-1,3-thiazolane-2,4-dione C26H31NO6S 详情 详情
(XI) 44683 5-(4-[[6-(methoxymethoxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methoxy]benzyl)-1,3-thiazolidine-2,4-dione C26H31NO6S 详情 详情
Extended Information