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【结 构 式】

【分子编号】44388

【品名】4-hydroxy-1,4-bis(3,4,5-trimethoxyphenyl)-1-butanone

【CA登记号】

【 分 子 式 】C22H28O8

【 分 子 量 】420.45952

【元素组成】C 62.85% H 6.71% O 30.44%

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:(VIII)

Synthesis of intermediate 1,4-bis(3,4,5-trimethoxyphenyl)butane-1,4-dione (V). This compound can be obtained by three related methods: 1. The Grignard reaction of 3,4,5-trimethoxybenzaldehyde (I) with vinylmagnesium bromide (II), followed by oxidation with MnO2, gives 1-(3,4,5-trimethoxyphenyl)-2-propen-1-one (III), which is then condensed with aldehyde (I) by means of the thiazolium salt (IV) to yield the target intermediate (V). 2. The condensation of 3,4,5-trimethoxyacetophenone (VI) with methylamine and formaldehyde gives 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)-1-propanone (VII), which is treated with methyl iodide at 80 C to afford the previously reported propenone intermediate (III). 3.The direct dimerization of acetophenone (VI) by means of LDA and CuCl2 also gives the target intermediate (V). Synthesis of the target compound: The reduction of the butanedione intermediate (V) with LiAlH4 or NaBH4 gives (RS,RS)-1,4-bis(3,4,5-trimethoxyphenyl)butane-2,3-diol (IX), which is dehydrated to the target tetrahydrofuran by means of TFA, PdCl2/Cu(NO3)2 or MsCl/pyridine. Alternatively, the reduction of butanedione (V) can be performed stepwise, first with LiAlH(O-tBu)3 to give the intermediate hydroxyketone (VIII), which is reduced to the diol (IX). The isolation of the intermediate hydroxyketone (VIII) allows the separation of enantiomers offering the possibility of obtaining chiral forms of the target tetrahydrofuran.

1 Doebber, T.W.; Beattie, T.R.; Shen, T.-Y.; Hwang, S.-B.; Biftu, T. (Merck & Co., Inc.); New 2,5-diaryl tetrahydrofurans and analogs thereof as PAF antagonists. AU 8656430; EP 0199324; ES 8801909; JP 1987000077 .
2 Biftu, T.; Chabala, J.C.; Acton, J.; Kuo, C.-H.; Stevenson, R.; 2,5-DIARYLTETRAHYDROFURANS: PAF ANTAGONISTS. Drugs Fut 1989, 14, 4, 359.
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) 11136 3,4,5-Trimethoxybenzaldehyde 86-81-7 C10H12O4 详情 详情
(II) 16524 bromo(vinyl)magnesium 1826-67-1 C2H3BrMg 详情 详情
(III) 27941 1-(3,4,5-trimethoxyphenyl)-2-propen-1-one C12H14O4 详情 详情
(IV) 44365 3,4-diethyl-5-(2-hydroxyethyl)-1,3-thiazol-3-ium bromide C9H16BrNOS 详情 详情
(V) 44387 1,4-bis(3,4,5-trimethoxyphenyl)-1,4-butanedione C22H26O8 详情 详情
(VI) 44362 1-(3,4,5-trimethoxyphenyl)-1-ethanone 1136-86-3 C11H14O4 详情 详情
(VII) 44363 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)-1-propanone C14H21NO4 详情 详情
(VIII) 44388 4-hydroxy-1,4-bis(3,4,5-trimethoxyphenyl)-1-butanone C22H28O8 详情 详情
(IX) 44389 (1R,4R)-1,4-bis(3,4,5-trimethoxyphenyl)-1,4-butanediol C22H30O8 详情 详情
Extended Information