Hydroxysuccinic acid; Malic acid; Hydroxybutanedioic acid -Drug Synthesis Database

【结构式】

【分子编号】22743

【品名】Hydroxysuccinic acid; Malic acid; Hydroxybutanedioic acid

【CA登记号】617-48-1

【分子式】C₄H₆O₅

【分子量】134.08864

【元素组成】C 35.83% H 4.51% O 59.66%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IV)

By cyclocondensation of 3-nitrobenzaldehyde (I) with methyl 3-aminocrotonate (II) and 1-benzyl-3-(acetoacetoxy)pyrrolidine (III) in refluxing isopropanol. The pyrrolidine (III) is obtained as follows: The condensation of 2-hydroxysuccinic acid (IV) with benzylamine (VI), which is reduced with LiAlH4 in dry THF yielding N-benzyl-3-hydroxypyrrolidine (VIII). Finally, this compound is condensed with diketene (VII) by means of sodium acetate at 80 C.

参考文献中间体

合成目标

【1】 Tamazawa, K.; Takeuchi, M.; Arima, H.; Synthesis of 14C-and 2H-labeled (3S)-1-benzyl-3-py. J Label Compd Radiopharm 1988, 25, 2, 161.
【2】 Kojima, T.; Takenaka, T. (Yamanouchi Pharmaceutical Co., Ltd.); 1,4-Dihydropyridine-3,5-dicarboxylic acid ester de. DE 2904552; US 4220649 .
【3】 Prous, J.; Castaner, J.; YM-09730-5. Drugs Fut 1988, 13, 7, 634.

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)	12646	3-Nitrobenzaldehyde	99-61-6	C₇H₅NO₃	详情	详情
(II)	11372	Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate		C₅H₉NO₂	详情	详情
(III)	22742	2-Oxobutyric acid 1-benzylpyrrolidin-3-yl ester		C₁₅H₁₉NO₃	详情	详情
(IV)	22743	Hydroxysuccinic acid; Malic acid; Hydroxybutanedioic acid	617-48-1	C₄H₆O₅	详情	详情
(V)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(VI)	22745	1-Benzyl-3-hydroxypyrrolidine-2,5-dione		C₁₁H₁₁NO₃	详情	详情
(VII)	22746	1-benzyl-3-pyrrolidinol		C₁₁H₁₅NO	详情	详情
(VIII)	11367	4-Methylene-2-oxetanone; Acetyl ketene	674-82-8	C₄H₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

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

合成路线3

该中间体在本合成路线中的序号：(A)

Hydroquinone (I) is converted to 1,2,4-triacetoxybenzene (II), which is condensed with malic acid (A) to afford 6,7-dihydroxycoumarin (aesculetin) (III). This is methylated with dimethyl sulfate in acetone to give Scoparone.

参考文献中间体

合成目标

【1】 Arya, V.P.; Scoparone. Drugs Fut 1978, 3, 7, 550.
【2】 Singh, G.B.; et al.; J Sci Ind Res 1956, 15, 19, Suppl. 2, 190-193.
【3】 King, F.E.; et al.; J Chem Soc 1954, 106, 19, Suppl. 2, 1392-99.
【4】 Thakur, R.S.; et al.; Res and Ind 1975, 3, 19, Suppl. 2, 129-131.
【5】 DuH, S.B.; Parihar, D.B.; Proc Ind Acad Sci 1947, 106, 19, Suppl. 2, 153.
【6】 Stefanovic, M.; et al.; Phytochem 1973, 12, 19, Suppl. 2, 2996.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	22743	Hydroxysuccinic acid; Malic acid; Hydroxybutanedioic acid	617-48-1	C₄H₆O₅	详情	详情
(I)	13163	p-Dihydrobenzene; Hydroquinone	123-31-9	C₆H₆O₂	详情	详情
(II)	39904	1,2,4-Triacetoxybenzene; 2,4-bis(acetoxy)phenyl acetate	613-03-6	C₁₂H₁₂O₆	详情	详情
(III)	39905	6,7-dihydroxy-2H-chromen-2-one	305-01-1	C₉H₆O₄	详情	详情

Extended Information