4-(hydroxymethyl)-5-methyl-1,3-dioxol-2-one -Drug Synthesis Database

【结构式】

【分子编号】50468

【品名】4-(hydroxymethyl)-5-methyl-1,3-dioxol-2-one

【CA登记号】

【分子式】C₅H₆O₄

【分子量】130.10024

【元素组成】C 46.16% H 4.65% O 49.19%

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：(XXV)

Treatment of 4-(chloromethyl)-5-methyl-1,3-dioxol-2-one (XXII) with potassium formate (XXIII) by means of KI and NaHCO3 in DMF affords the formyloxymethyl derivative (XXIV), which is converted into the hydroxymethyl derivative (XXV) by refluxing in MeOH. Coupling of compound (XXV) with oxalyl chloride (XXVI) in dichloromethane furnishes compound (XXVII), which is then condensed with protected azetidinone (VI) by means of Et3N in dichloromethane to yield compound (XXVIII). Intramolecular Wittig cyclization of compound (XXVIII) by means of triethyl phosphite in refluxing xylene provides the silylated faropenem daloxate (XXIX), which is finally deprotected by means of either Et3N tris(hydrogen fluoride) in ethyl acetate or tetrabutylammonium fluoride (TBAF) and AcOH in THF.

参考文献中间体

合成目标

【1】 Rabasseda, X.; Sorbera, L.A.; del Fresno, M.; Castaner, J.; Faropenem daloxate. Drugs Fut 2002, 27, 3, 223.
【2】 Ishiguro, M.; Kanebo, A.; Kaku, T.; Nakatsuka, T. (Nippon Soda Co., Ltd.; Suntory Ltd.); Method of desilylating silylether cpds.. EP 0612749 .
【3】 Fukami, H.; Shima, K.; Nakatsuka, T.; Iwata, H.; Yoshida, T.; Mizukawa, Y.; Shibata, M.; Sekiuchi, K.; Iwanami, T. (Suntory Ltd.); Preparation method of penem derivs.. JP 1994192270 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	11689	S-[(2R,3S)-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxoazetanyl] (2R)tetrahydro-2-furancarbothioate		C₁₆H₂₉NO₄SSi	详情	详情
(XXII)	16911	4-(chloromethyl)-5-methyl-1,3-dioxol-2-one		C₅H₅ClO₃	详情	详情
(XXIII)	52172	Potassium formate; Formic acid potassium salt	590-29-4	CHKO₂	详情	详情
(XXIV)	50467	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl formate		C₆H₆O₅	详情	详情
(XXV)	50468	4-(hydroxymethyl)-5-methyl-1,3-dioxol-2-one		C₅H₆O₄	详情	详情
(XXVI)	29841	Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride	79-37-8	C₂Cl₂O₂	详情	详情
(XXVII)	52173	2-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy]-2-oxoacetyl chloride		C₇H₅ClO₆	详情	详情
(XXVIII)	52174	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-((3S,4R)-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-2-oxo-4-[[(2R)tetrahydro-2-furanylcarbonyl]sulfanyl]azetidinyl)-2-oxoacetate		C₂₃H₃₃NO₁₀SSi	详情	详情
(XXIX)	52175	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (5R,6S)-6-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-7-oxo-3-[(2R)tetrahydro-2-furanyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₃H₃₃NO₈SSi	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The acylating reagent (V) was prepared as follows. Allylic bromination of 4,5-dimethyl-1,3-dioxolene-2-one (I) with N-bromosuccinimide afforded bromide (II). This was converted to alcohol (IV) via formation of the formate ester (III), followed by acidic hydrolysis. Reaction of (IV) with p-nitrophenyl chloroformate and pyridine furnished carbonate (V). The acylation of pseudomycin B (VI) with carbonate (V) produced a mixture of mono-, di- and triacylated compounds from which the desired tricarbamate was isolated by reverse-phase preparative HPLC.

参考文献中间体

合成目标

【1】 Sun, X.; et al.; Synthesis and evaluation of oxodioxolenylmethyl carbamate prodrugs of pseudomycins. J Med Chem 2001, 44, 16, 2671.
【2】 Chen, S.H.; Sun, X.D.; Rodriguez, M.J. (Eli Lilly and Company); Pseudomycin prodrugs. WO 0105813 .

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)	31106	4,5-dimethyl-1,3-dioxol-2-one	37830-90-3	C₅H₆O₃	详情	详情
(II)	13462	4-(Bromomethyl)-5-methyl-1,3-dioxol-2-one	80715-22-6	C₅H₅BrO₃	详情	详情
(III)	50467	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl formate		C₆H₆O₅	详情	详情
(IV)	50468	4-(hydroxymethyl)-5-methyl-1,3-dioxol-2-one		C₅H₆O₄	详情	详情
(V)	25503	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonate		C₁₂H₉NO₈	详情	详情
(VI)	50469	(2S)-2-((3S,6S,12S,15S,18S,21S,24R,27S)-18-(4-aminobutyl)-15,24-bis(2-aminoethyl)-21-(carboxymethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-9-[(Z)ethylidene]-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxytetradecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octaazacyclooctacosan-6-yl)-2-hydroxyethanoic acid		C₅₁H₈₇ClN₁₂O₁₉	详情	详情

Extended Information