acetone oxime; Acetoxime -Drug Synthesis Database

【结构式】

【分子编号】17791

【品名】acetone oxime; Acetoxime

【CA登记号】127-06-0

【分子式】C₃H₇NO

【分子量】73.09472

【元素组成】C 49.3% H 9.65% N 19.16% O 21.89%

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：(VI)

Treatment of 4-hydroxy-3-methoxybenzoic acid (I) with thionyl chloride and then with diisopropyl amine provided amide (II). Alkylation of (II) with 1,4-dibromobutane and potassium carbonate in acetonitrile, followed by treatment with sodium iodide afforded iodobutylether (III). Then, alkylation of 2-fluoro-4-hydroxybenzonitrile (IV) with iodide (III) in the presence of sodium hydride in DMF gave (V), which was condensed with acetone oxime (VI) and potassium tert-butoxide to provide (VII). Finally, cyclization of (VII) in a refluxing hydroalcoholic solution of HCl generated the target benzisoxazole.

参考文献中间体

合成目标

【1】 Suh, H.; et al.; 3-Amino-1,2-benzisoxazoles: A new family of potent inhibitors of LTB4 binding to the human neutrophils. Bioorg Med Chem Lett 1997, 7, 4, 389.

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)	17786	4-hydroxy-3-methoxybenzoic acid; Vanillic acid	121-34-6	C₈H₈O₄	详情	详情
(II)	17787	4-hydroxy-N,N-diisopropyl-3-methoxybenzamide		C₁₄H₂₁NO₃	详情	详情
(III)	17788	4-(4-iodobutoxy)-N,N-diisopropyl-3-methoxybenzamide		C₁₈H₂₈INO₃	详情	详情
(IV)	17789	2-Fluoro-4-hydroxybenzonitrile	82380-18-5	C₇H₄FNO	详情	详情
(V)	17790	4-[4-(4-cyano-3-fluorophenoxy)butoxy]-N,N-diisopropyl-3-methoxybenzamide		C₂₅H₃₁FN₂O₄	详情	详情
(VI)	17791	acetone oxime; Acetoxime	127-06-0	C₃H₇NO	详情	详情
(VII)	17792	4-[4-(4-cyano-3-[[(1-methylethylidene)amino]oxy]phenoxy)butoxy]-N,N-diisopropyl-3-methoxybenzamide		C₂₈H₃₇N₃O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of 2-fluoronitrobenzene (I) with acetone oxime (II) by means of NaH in DMF gives acetone O-(2-nitrophenyl)oxime (III), which is cyclized to 2-methyl-7-nitrobenzofuran (IV) by means of H2SO4. The Friedel Crafts acylation of (IV) with acetyl chloride and AlCl3 in dichloromethane affords 3-acetyl-2-methyl-7-nitrobenzofuran (V), which is reduced to the corresponding amino derivative (VI) with Fe and HCl in ethanol. The condensation of (VI) with 2,6-dichlorobenzoyl chloride (VII) by means of triethylamine in dichloroethane yields N-(3-acetyl-2-methylbenzofuran-7-yl)-2,6-dichlorobenzamide (VIII), which is finally submitted to a Grignard reaction with methylmagnesium bromide in THF.

参考文献中间体

合成目标

【1】 Yamazaki, H.; et al.; Synthesis and pharmacological activities of novel benzofuran derivatives as vacuolar type H+-ATPase inhibitors. Symp Med Chem 1998, Abst 2-P-32.
【2】 Kawai, Y.; Yamazaki, H.; Kayakiri, N.; Yoshihara, K.; Yatabe, T.; Oku, T. (Fujisawa Pharmaceutical Co., Ltd.); Benzofuran derivs. useful as inhibitors of bone resorption. EP 0757682; JP 1997512795; US 5858995; WO 9529907 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	19273	acetyl chloride	75-36-5	C₂H₃ClO	详情	详情
(I)	13463	o-Fluoronitrobenzene; 1-fluoro-2-nitrobenzene	1493-27-2	C₆H₄FNO₂	详情	详情
(II)	17791	acetone oxime; Acetoxime	127-06-0	C₃H₇NO	详情	详情
(III)	25083	acetone O-(2-nitrophenyl)oxime		C₉H₁₀N₂O₃	详情	详情
(IV)	25084	2-methyl-7-nitro-1-benzofuran		C₉H₇NO₃	详情	详情
(V)	25086	1-(7-amino-2-methyl-1-benzofuran-3-yl)-1-ethanone		C₁₁H₁₁NO₂	详情	详情
(VI)	24086	benzhydryl 2-[[2-(tert-butoxy)-2-oxoethoxy]imino]-2-[2-(formylamino)-1,3-thiazol-4-yl]acetate		C₂₅H₂₅N₃O₆S	详情	详情
(VII)	25087	2,6-dichlorobenzoyl chloride	4659-45-4	C₇H₃Cl₃O	详情	详情
(VIII)	25088	N-(3-acetyl-2-methyl-1-benzofuran-7-yl)-2,6-dichlorobenzamide		C₁₈H₁₃Cl₂NO₃	详情	详情

Extended Information