sodium 4-hydroxybutanoate -Drug Synthesis Database

【结构式】

【分子编号】34856

【品名】sodium 4-hydroxybutanoate

【CA登记号】502-85-2

【分子式】C₄H₇NaO₃

【分子量】126.087548

【元素组成】C 38.1% H 5.6% Na 18.23% O 38.07%

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：(XLII)

Sodium 4-hydroxybutyrate (XLII) was diben-zylated to give (XLIII), and then hydrolyzed with NaOH yielding 4-benzyl-oxybutyric acid (XLIV). Coupling of (XLIV) with alcohol (XXXII) then afforded ester (XLV). Deprotection of the benzyl ether of (XLV) by transfer hydrogenation with HCOOH and Pd catalyst produced hydroxy ester (XLVI). The precursor dibenzyl phosphate (XLI) was then obtained by coupling of (XLVI) with N,N-diisopropyl dibenzyl phosphoramidite, followed by oxidation of the intermediate phosphite with tertbutyl hydroperoxide. Finally, the hydrogenolysis of the benzyl groups of (XLI) as above furnished the title compound.

参考文献中间体

合成目标

【1】 Bennett, F.; Girijavallabhan, V.M.; Patel, N.M.; Ganguly, A.; Saksena, A.K. (Schering Corp.); Tetrahydrofuran phosphate- and hydroxy esters, as prodrugs for the corresponding antifungal agent. EP 1027349; WO 9915522 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情
	40602			C₁₇H₂₂NO₃P	详情	详情
(XXXII)	34850	4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-2-[(1S,2S)-1-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one		C₃₇H₄₂F₂N₈O₄	详情	详情
(XLI)	34855	(1S,2S)-2-(4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-1-methylbutyl 4-[[bis(benzyloxy)phosphoryl]oxy]butanoate		C₅₅H₆₁F₂N₈O₉P	详情	详情
(XLII)	34856	sodium 4-hydroxybutanoate	502-85-2	C₄H₇NaO₃	详情	详情
(XLIII)	34857	benzyl 4-(benzyloxy)butanoate		C₁₈H₂₀O₃	详情	详情
(XLIV)	34858	4-(benzyloxy)butyric acid		C₁₁H₁₄O₃	详情	详情
(XLV)	34859	(1S,2S)-2-(4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-1-methylbutyl 4-(benzyloxy)butanoate		C₄₈H₅₄F₂N₈O₆	详情	详情
(XLVI)	34860	(1S,2S)-2-(4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-1-methylbutyl 4-hydroxybutanoate		C₄₁H₄₈F₂N₈O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The esterification of sodium 4-hydroxybutyrate (I) with 4-nitrobenzyl chloride (II) gives the corresponding ester (III), which is condensed with dibenzyl chlorophosphate (III) in pyridine, yielding the expected phosphoric ester (IV). The cleavage of the 4-nitrobenzyl ester of (IV) with Na2S or Zn/HCl affords the butyric acid derivative (V), which is condensed with SCH-56592 (VI) by means of DMAP and Ts-Cl to provide the corresponding ester (VII). Finally, the benzyl groups of the phosphate moiety of (VII) are cleaved by hydrogenation with H2 or HCOOH over Pd/C in THF, giving rise to the target SCH-59884.

参考文献中间体

合成目标

【1】 Lee, G.M.; et al.; Synthesis of injectable antifungal Sch 59884. Org Process Res Dev 2001, 5, 6, 622.
【2】 Lee, G.M.; et al.; Synthesis of injectable antifungal Sch 59884. (Erratum). Org Process Res Dev 2002, 6, 1, 86.

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)	34856	sodium 4-hydroxybutanoate	502-85-2	C₄H₇NaO₃	详情	详情
(II)	52647	(4-nitrophenyl)methyl 4-hydroxybutanoate		C₁₁H₁₃NO₅	详情	详情
(III)	52648	Chlorophosphoric acid dibenzyl ester; Dibenzylphosphoryl chloride	538-37-4	C₁₄H₁₄ClO₃P	详情	详情
(IV)	52649	(4-nitrophenyl)methyl 4-({bis[(phenylmethyl)oxy]phosphoryl}oxy)butanoate		C₂₅H₂₆NO₈P	详情	详情
(V)	52650	4-({bis[(phenylmethyl)oxy]phosphoryl}oxy)butanoic acid		C₁₈H₂₁O₆P	详情	详情
(VI)	52651	1-(4-{4-[4-({[5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methyl}oxy)phenyl]-1-piperazinyl}phenyl)-3-(1-ethyl-2-hydroxypropyl)-1,3-dihydro-2H-imidazol-2-one		C₃₈H₄₃F₂N₇O₄	详情	详情
(VII)	52652	2-[3-(4-{4-[4-({[5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methyl}oxy)phenyl]-1-piperazinyl}phenyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-1-methylbutyl 4-({bis[(phenylmethyl)oxy]phosphoryl}oxy)butanoate		C₅₆H₆₂F₂N₇O₉P	详情	详情

Extended Information