bromo(2-ethylbutyl)magnesium -Drug Synthesis Database

【结构式】

【分子编号】57441

【品名】bromo(2-ethylbutyl)magnesium

【CA登记号】

【分子式】C₆H₁₃BrMg

【分子量】189.37822

【元素组成】C 38.05% H 6.92% Br 42.19% Mg 12.83%

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：(VII)

In an alternative procedure, the known hydroxynaphthalene dicarboxylate (I) is protected as the methoxymethyl ether (III) using chloromethyl methyl ether (II) and diisopropyl ethylamine. Subsequent partial hydrolysis of diester (III) with KOH leads to acid (IV). Removal of the methoxymethyl protecting group of (IV) to produce naphthol (V) is accomplished by treatment with in situ generated iodotrimethylsilane. Hydroxy acid (V) is then converted to the dioxinone derivative (VI) employing diiodomethane and CsF in hot DMF. Finally, addition of the Grignard reagent (VII) to the lactone function of (VI) yields the desired 2-ethylbutyl ketone.

参考文献中间体

合成目标

【1】 Mori, S.; Takechi, S.; Kida, S.; Mizui, T.; Ichihashi, T. (Shionogi & Co. Ltd.); Lignan analog, production thereof, and hypolipidemic drug. EP 0597107; EP 0701991; JP 1993310634; US 5731455; WO 9308155 .

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)	57436	dimethyl 4-(3,4-dimethoxyphenyl)-1-hydroxy-5,6,7-trimethoxy-2,3-naphthalenedicarboxylate		C₂₅H₂₆O₁₀	详情	详情
(II)	18319	Chloro(methoxy)methane; Chloromethyl methyl ether	107-30-2	C₂H₅ClO	详情	详情
(III)	57437	dimethyl 4-(3,4-dimethoxyphenyl)-5,6,7-trimethoxy-1-(methoxymethoxy)-2,3-naphthalenedicarboxylate		C₂₇H₃₀O₁₁	详情	详情
(IV)	57438	4-(3,4-dimethoxyphenyl)-5,6,7-trimethoxy-3-(methoxycarbonyl)-1-(methoxymethoxy)-2-naphthoic acid		C₂₆H₂₈O₁₁	详情	详情
(V)	57439	4-(3,4-dimethoxyphenyl)-1-hydroxy-5,6,7-trimethoxy-3-(methoxycarbonyl)-2-naphthoic acid		C₂₄H₂₄O₁₀	详情	详情
(VI)	57440	methyl 6-(3,4-dimethoxyphenyl)-7,8,9-trimethoxy-4-oxo-4H-naphtho[1,2-d][1,3]dioxine-5-carboxylate		C₂₅H₂₄O₁₀	详情	详情
(VII)	57441	bromo(2-ethylbutyl)magnesium		C₆H₁₃BrMg	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

In a related procedure, malic acid (I) is converted into the O-acetylated monomethyl ester (IV) by a sequence involving O-acetylation with acetic anhydride, followed by dehydration of the resultant O-acetyl malic acid (II) to the cyclic anhydride (III), which undergoes further methanolysis to mono ester (IV). Mono-acid (IV) is then chlorinated with SOCl2, yielding acid chloride (V). Subsequent Li2CuCl4-catalyzed cross-coupling of acid chloride (V) with 2-ethylbutylmagnesium bromide (VI) affords ketone (VII). Elimination of the acetate group of (VII) with triethylamine in toluene leads to the acyl propenoate (VIII). This is subjected to cycloaddition reaction with the lithium derivative of phthalide (IX) producing the dihydroxydihydronaphthalene adduct (X). Finally, dehydration of (X) under acidic conditions furnishes the title compound.

参考文献中间体

合成目标

【1】 Mori, S.; et al.; Convergent synthesis of S-8921, a new potent hypocholesterolemic arylnapththalene lignan analog. Tetrahedron Lett 1999, 40, 6, 1165.

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)	22743	Hydroxysuccinic acid; Malic acid; Hydroxybutanedioic acid	617-48-1	C₄H₆O₅	详情	详情
(II)	57448	2-(acetyloxy)succinic acid		C₆H₈O₆	详情	详情
(III)	57449	2,5-dioxotetrahydro-3-furanyl acetate		C₆H₆O₅	详情	详情
(IV)	57450	3-(acetyloxy)-4-methoxy-4-oxobutanoic acid		C₇H₁₀O₆	详情	详情
(V)	57451	methyl 2-(acetyloxy)-4-chloro-4-oxobutanoate		C₇H₉ClO₅	详情	详情
(VI)	57441	bromo(2-ethylbutyl)magnesium		C₆H₁₃BrMg	详情	详情
(VII)	57452	methyl 2-(acetyloxy)-6-ethyl-4-oxooctanoate		C₁₃H₂₂O₅	详情	详情
(VIII)	57453	methyl (E)-6-ethyl-4-oxo-2-octenoate		C₁₁H₁₈O₃	详情	详情
(IX)	57443	3-(3,4-dimethoxyphenyl)-4,5,6-trimethoxy-2-benzofuran-1(3H)-one		C₁₉H₂₀O₇	详情	详情
(X)	57454	methyl (1S,2R)-1-(3,4-dimethoxyphenyl)-3-(3-ethylpentanoyl)-1,4-dihydroxy-6,7,8-trimethoxy-1,2-dihydro-2-naphthalenecarboxylate		C₃₀H₃₈O₁₀	详情	详情

Extended Information