dimethyl succinate -Drug Synthesis Database

【结构式】

【分子编号】41056

【品名】dimethyl succinate

【CA登记号】106-65-0

【分子式】C₆H₁₀O₄

【分子量】146.143

【元素组成】C 49.31% H 6.9% O 43.79%

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：(I)

The condensation of dimethyl succinate (I) with benzaldehyde (II) by means of NaOMe in refluxing methanol followed by hydrolysis with NaOH in methanol/water gives 2-benzylidenesuccinic acid (III). Compound (III) is treated with refluxing Ac2O, yielding the corresponding anhydride (IV), which by reaction with cis-perhydroisoindole (V) in toluene affords the monoamide (VI). This amide is reduced with H2 over a chiral Rhodium catalyst and treated with (R)-1-phenylethylamine (VII) to provide the chiral salt (VIII) as a single diastereomer isolated by crystallization. Finally, this salt is treated first with aqueous NH4OH and then with aqueous CaCl2.

参考文献中间体

合成目标

【1】 Castaner, R.M.; Sorbera, L.A.; Leeson, P.A.; Castaner, J.; Mitiglinide Calcium Hydrate. Drugs Fut 2000, 25, 10, 1034.
【2】 Lecouve, J.-P.; Souvie, J.-C.; Fugier, C. (ADIR et Cie.); Method for preparing a substd. perhydroisoindole. FR 2765578; US 6133454; WO 9901430 .

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)	41056	dimethyl succinate	106-65-0	C₆H₁₀O₄	详情	详情
(II)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(III)	41057	2-[(Z)-benzylidene]succinic acid		C₁₁H₁₀O₄	详情	详情
(IV)	41058	3-[(Z)-benzylidene]-2,5(4H)-furandione		C₁₁H₈O₃	详情	详情
(V)	41059	(3aR,7aS)octahydro-1H-isoindole		C₈H₁₅N	详情	详情
(VI)	41060	(Z)-2-[2-[(3aR,7aS)octahydro-2H-isoindol-2-yl]-2-oxoethyl]-3-phenyl-2-propenoic acid		C₁₉H₂₃NO₃	详情	详情
(VII)	10039	(1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine	3886-69-9	C₈H₁₁N	详情	详情
(VIII)	41061	(1R)-1-phenyl-1-ethanaminium (2S)-4-[(3aR,7aS)octahydro-2H-isoindol-2-yl]-2-benzyl-4-oxobutanoate		C₂₇H₃₆N₂O₃	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 4-iodo-1,3-benzodioxole-5-carbaldehyde (I) with dimethyl succinate (II) by means of NaOMe in aqueous methanol gives the benzylidene derivative (III), which is condensed with 1,3-benzodioxole-5-carbaldehyde (IV) by means of NaOMe in methanol, affording the bis-benzylidene hemiester (V). The selective reduction of (V) with LiEt3BH, followed by lactonization with ethyl chloroformate and TEA in THF, yields the lactone (VI), which is finally cyclized by means of Pd(OAc)2 and K2CO3 at 110 C through the nonisolated intermediate (VII), providing the target compound.

参考文献中间体

合成目标

【1】 Mizufune, H.; et al.; The first regiospecific synthesis of helioxanthin by novel palladium-catalyzed benzannulation reaction of alpha,beta-bisbenzylidene-gamma-lactone. Tetrahedron Lett 2001, 42, 3, 437.

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)	46632	4-iodo-1,3-benzodioxole-5-carbaldehyde		C₈H₅IO₃	详情	详情
(II)	41056	dimethyl succinate	106-65-0	C₆H₁₀O₄	详情	详情
(III)	46633	dimethyl 2-[(E)-(4-iodo-1,3-benzodioxol-5-yl)methylidene]succinate		C₁₄H₁₃IO₆	详情	详情
(IV)	10127	1,3-Benzodioxole-5-carbaldehyde; Heliotropine	120-57-0	C₈H₆O₃	详情	详情
(V)	46634	(E)-4-(1,3-benzodioxol-5-yl)-2-[(E)-(4-iodo-1,3-benzodioxol-5-yl)methylidene]-3-(methoxycarbonyl)-3-butenoic acid		C₂₁H₁₅IO₈	详情	详情
(VI)	46635	4-[(E)-1,3-benzodioxol-5-ylmethylidene]-3-[(E)-(4-iodo-1,3-benzodioxol-5-yl)methylidene]dihydro-2(3H)-furanone		C₂₀H₁₃IO₆	详情	详情
(VII)	46636	[(10S)-10-(1,3-benzodioxol-5-yl)-7-oxo-7,10-dihydrofuro[3',4':6,7]naphtho[1,2-d][1,3]dioxol-9(9H)-yl](iodo)palladium		C₂₀H₁₃IO₆Pd	详情	详情

Extended Information