(2R,3R)-2,3-bis(benzoyloxy)butanedioic acid -Drug Synthesis Database

【结构式】

【分子编号】16186

【品名】(2R,3R)-2,3-bis(benzoyloxy)butanedioic acid

【CA登记号】

【分子式】C₁₈H₁₄O₈

【分子量】358.30436

【元素组成】C 60.34% H 3.94% O 35.72%

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：(IX)

1) The reaction of dimethyl sulfate (I) with dimethyl sulfide (II) by means of sodium methoxide in acetonitrile gives dimethyl (methylene)-lambda4-sulfane (III), which, without isolation, is condensed with benzo[b]thiophene-5-carbaldehyde (IV) in the same solvent to yield 2-(benzo[b]thiophen-5-yl)oxirane (V) (1). The reaction of (V) with 2-(dimethylamino)ethanol (VI) by means of potassium tert-butoxide in hot DMSO (1, 2), or hot DMF (3) affords (±)-1-(benzo[b]thiophen-5-yl)-2-[2-(diethylamino)ethoxy]ethanol (racemic T-588) (VII), which is submitted to optical resolution first by treatment with acetic anhydride in refluxing toluene to give the corresponding acetate (VIII), and then by reaction of (VIII) with D-dibenzoyltartaric acid (IX) in ethyl acetate/acetone/water followed by fractionated crystallization of the resulting salt to yield the D-dibenzoyltartrate salt of the (R)-isomer (X). Finally, (X) is deacetylated with sodium methoxide in methanol and salified with ethanolic hydrochloric acid.

参考文献中间体

合成目标

【1】 Ono, S.; Yamafuji, T.; Chaki, H.; Todo, Y.; Maekawa, M.; Kitamura, K.; Kimura, T.; Nakada, Y.; Mozumi, K.; Narita, H.; A new cognition-enhancing agent, (R)-(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino)ethoxy]ethanol hydrochloride. Effects on memory impairment in rats generated by cerebral embolization and basal forebrain lesions. Biol Pharm Bull 1995, 18, 12, 1779-83.
【2】 Ono, S.; Yamafuji, T.; Chaki, H.; Morita, H.; Todo, Y.; Okada, N.; Maekawa, M.; Kitamura, K.; Tai, M.; Narita, H.; Studies on cognitive enhancing agents. III. Antiamnestic and antihypoxic activities of a series of 1-bicycloaryl-2-(omega-aminoalkoxy)ethanols. Chem Pharm Bull 1995, 43, 9, 1492-6.
【3】 Martel, A.M.; Prous, J.; Castaner, J.; T-588. Drugs Fut 1997, 22, 4, 386.
【4】 Ono, S.; Yamafuji, T.; Chaki, H.; Maekawa, M.; Todo, Y.; Narita, H. (Toyama Chemical Co., Ltd.); 1,2-Ethanediol deriv. and salt thereof, process for producing the same, and cerebral function-improving agent comprising them. EP 0383281; EP 0587193; EP 0587194; EP 0589484; FR 2643079; JP 1991047158; JP 1991197422; US 5280032; US 5472984; US 5612381; US 5658904 .
【5】 Ono, T.; Yamafuji, T.; Chaki, H.; Maekawa, M.; Fujido, Y.; Narita, H. (Toyama Chemical Co., Ltd.); 1,2-Ethanediol derivs. and their salts. JP 1992095070 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	16179	Dimethyl sulfide; (Methylsulfanyl)methane	75-18-3	C₂H₆S	详情	详情
(III)	16180	Dimethyl(methylene)-lambda(4)-sulfane; Dimethylsulfonium-methylide		C₃H₈S	详情	详情
(IV)	16181	1-benzothiophene-5-carbaldehyde		C₉H₆OS	详情	详情
(V)	16182	2-(1-benzothiophen-5-yl)oxirane		C₁₀H₈OS	详情	详情
(VI)	16183	Diethylaminoethanol; 2-(diethylamino)-1-ethanol	100-37-8	C₆H₁₅NO	详情	详情
(VII)	16184	1-(1-benzothiophen-5-yl)-2-[2-(diethylamino)ethoxy]-1-ethanol		C₁₆H₂₃NO₂S	详情	详情
(VIII)	16185	1-(1-benzothiophen-5-yl)-2-[2-(diethylamino)ethoxy]ethyl acetate		C₁₈H₂₅NO₃S	详情	详情
(IX)	16186	(2R,3R)-2,3-bis(benzoyloxy)butanedioic acid		C₁₈H₁₄O₈	详情	详情
(X)	16187	(1R)-1-(1-benzothiophen-5-yl)-2-[2-(diethylamino)ethoxy]ethyl acetate		C₁₈H₂₅NO₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The enantiomerically pure benzodioxane derivative (VIII) was obtained in a straightforward route including five steps starting from pyrocatechin (I). Racemic (VI) was then resolved by means of crystallization with (-)-O,O'-dibenzoyl-L-tartaric acid.

参考文献中间体

合成目标

【1】 Matyus, P.; GYKI-16084. Drugs Fut 1999, 24, 10, 1072.
【2】 3(2H)-Pyridazinone derivs. and pharmaceutical compsns. containing these cpds.. WO 9638441 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	18522	3-amino-1-propanol	156-87-6	C₃H₉NO	详情	详情
(I)	11599	o-Dihydroxybenzene; Catechol; Pyrocatechol	120-80-9	C₆H₆O₂	详情	详情
(II)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(III)	28714	2,3-dihydro-1,4-benzodioxin-2-ylmethanol	3663-82-9	C₉H₁₀O₃	详情	详情
(IV)	20959	2,3-dihydro-1,4-benzodioxin-2-ylmethyl 4-methylbenzenesulfonate		C₁₆H₁₆O₅S	详情	详情
(V)	20960	3-[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]-1-propanol		C₁₂H₁₇NO₃	详情	详情
(VI)	28715	3-chloro-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-propanamine		C₁₂H₁₆ClNO₂	详情	详情
(VII)	16186	(2R,3R)-2,3-bis(benzoyloxy)butanedioic acid		C₁₈H₁₄O₈	详情	详情
(VIII)	28716	3-chloro-N-[(2R)-2,3-dihydro-1,4-benzodioxin-2-ylmethyl]-1-propanamine		C₁₂H₁₆ClNO₂	详情	详情

Extended Information