2,3-butanediol -Drug Synthesis Database

【结构式】

【分子编号】24048

【品名】2,3-butanediol

【CA登记号】513-85-9

【分子式】C₄H₁₀O₂

【分子量】90.1222

【元素组成】C 53.31% H 11.18% O 35.51%

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：(III)

The reaction of indomethacin (I) with SOCl2 in hot benzene gives the corresponding acyl chloride (II), which is then condensed with 2,3-butanediol (III) by means of pyridine in THF.

参考文献中间体

合成目标

【1】 Isomae, K.; Kuwamura, T.; Mogi, K.; Ogawa, Y.; Sato, S. (SSP Co., Ltd.); Esters of indomethacin. DE 3235850; GB 2125786 .
【2】 Prous, J.; Castaner, J.; SY-6001. Drugs Fut 1986, 11, 3, 194.

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)	22930	2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid		C₁₉H₁₆ClNO₄	详情	详情
(II)	24047	2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl chloride		C₁₉H₁₅Cl₂NO₃	详情	详情
(III)	24048	2,3-butanediol	513-85-9	C₄H₁₀O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：

12) The ketalization of (R)-2-(2-oxocyclopentyl)acetic acid methyl ester (XCVII) with butane-2,3-diol gives the expected acetal (XCVIII), which is converted into the beta-keto ester (XCIX) in the usual way. Transesterification of (XCIX) with benzyl alcohol yields the benzyl ester (C), which is converted into the alpha-diazo ester (CI) with p-toluenesulfonyl azide. The cyclization of (CI) by means of rhodium acetate in dichloromethane affords the bicyclic keto ester (CII), which is condensed with 3(S)-(TBDMS-O)-1(E)-octenyl mercury (CIII) by means of lead tetraacetate giving the alkylated bicyclic beta-keto ester (CIV). The decarboxylation of (CIV) with Raney Ni and triethylamine in ethanol yields the bicyclic ketone (CV), which is reduced with NaBH4 and deacetalized with HCl to afford the hydroxy ketone (CVI). The silylation of the hydroxy group of (CVI) with TBDMS-Cl and DMAP in DMF gives the disilylated ketone (CVII), which is treated with diphenyl disulfide and lithium bis(trimethylsilyl)amide in THF/HMPT yielding the sulfenylated enol (CVIII). The oxidation of (CVIII) with m-chloroperbenzoic acid (MCPBA) affords the corresponding sulfonated enol (CIX), which is condensed with methyl 4-iodobutyrate (CX) by means of t-BuOK in DMSO giving the dialkylated bicyclic ketone (CXI). The reduction of (CXI) with NaBH4 in methanol, followed by mesylation with mesyl chloride yields the alpha-mesyloxy sulfone (CXII), which by a reductive elimination with Na-Hg in methanol is converted into the bisilylated clinprost (XCIII). Finally, this compound is desilyated with TBAF as usual.

参考文献中间体

合成目标

【1】 Graul, A.; Leeson, P.; Castaner, J.; Clinprost. Drugs Fut 1997, 22, 6, 608.
【2】 Hashimoto, S.; Shinoda, T.; Ikegami, S.; A simple synthesis of (+)-isocarbacyclin via a convergent process. J Chem Soc Chem Commun 1988, 17, 1137-9.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	24048	2,3-butanediol	513-85-9	C₄H₁₀O₂	详情	详情
(CI)	13825	2-Diazo-4-[(6R)-2,3-dimethyl-1,4-dioxaspiro[4.4]non-6-yl]-3-oxobutyric acid benyzl ester		C₂₀H₂₄N₂O₅	详情	详情
(CII)	13826	(3'aS,6'aS)-4,5-Dimethyl-5'-oxoperhydrospiro[1,3-dioxolane-2,1'-pentalen]-4'-ylcarboxylic acid benzyl ester		C₂₀H₂₄O₅	详情	详情
(CIII)	13827	((E,3S)-3-[[tert-Butyl(dimethyl)silyl]oxy]-1-octenyl)mercury		C₁₄H₂₉HgOSi	详情	详情
(CIV)	13828	(3'aS,6'aS)-4,5-Dimethyl-4'-[3-[tert-butyl(dimethyl)silyloxy]-1(E)-octenyl]-5'-oxoperhydrospiro[1,3-dioxolane-2,1'-pentalen]-4'-ylcarboxylic acid benzyl ester		C₃₄H₅₂O₆Si	详情	详情
(CV)	13829	(3'aS,6'aS)-4,5-Dimethyl-4'-[3-[tert-butyl(dimethyl)silyloxy]-1(E)-octenyl]perhydrospiro[1,3-dioxolane-2,1'-pentalen]-5'-one		C₂₆H₄₆O₄Si	详情	详情
(CVI)	13830	(3aR,4R,5R,6aS)-4-((E,3S)-3-[[tert-Butyl(dimethyl)silyl]oxy]-1-octenyl)-5-hydroxyhexahydro-1(2H)-pentalenone		C₂₂H₄₀O₃Si	详情	详情
(CVII)	13831	(3aR,4R,5R,6aS)-5-[[tert-Butyl(dimethyl)silyl]oxy]-4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)hexahydro-1(2H)-pentalenone		C₂₈H₅₄O₃Si₂	详情	详情
(CVIII)	13832	(3aR,4R,5R,6aS)-5-[[tert-Butyl(dimethyl)silyl]oxy]-4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-2-(phenylsulfanyl)-3,3a,4,5,6,6a-hexahydro-1-pentalenol		C₃₄H₅₈O₃SSi₂	详情	详情
(CIX)	13833	(3aR,4R,5R,6aS)-5-[[tert-Butyl(dimethyl)silyl]oxy]-4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-2-(phenylsulfonyl)-3,3a,4,5,6,6a-hexahydro-1-pentalenol		C₃₄H₅₈O₅SSi₂	详情	详情
(CX)	13834	Methyl 5-iodovalerate; Methyl 5-iodopentanoate	14273-88-2	C₆H₁₁IO₂	详情	详情
(CXI)	13835	methyl 5-[(2R,3aR,4R,5R,6aS)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-1-oxo-2-(phenylsulfonyl)octahydro-2-pentalenyl]pentanoate		C₄₀H₆₈O₇SSi₂	详情	详情
(CXII)	13836	methyl 5-[(1R,2R,3aR,4R,5R,6aS)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-1-[(methylsulfonyl)oxy]-2-(phenylsulfonyl)octahydro-2-pentalenyl]pentanoate		C₄₁H₇₂O₉S₂Si₂	详情	详情
(XCIII)	13817	methyl 5-[(3aS,5R,6S,6aS)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]pentanoate		C₃₄H₆₄O₄Si₂	详情	详情
(XCVII)	13821	methyl 2-[(1R)-2-oxocyclopentyl]acetate		C₈H₁₂O₃	详情	详情
(XCVIII)	13822	methyl 2-[(6R)-2,3-dimethyl-1,4-dioxaspiro[4.4]non-6-yl]acetate		C₁₂H₂₀O₄	详情	详情
(XCIX)	13823	methyl 4-[(6R)-2,3-dimethyl-1,4-dioxaspiro[4.4]non-6-yl]-3-oxobutanoate		C₁₄H₂₂O₅	详情	详情
(C)	13824	benzyl 4-[(6R)-2,3-dimethyl-1,4-dioxaspiro[4.4]non-6-yl]-3-oxobutanoate		C₂₀H₂₆O₅	详情	详情

Extended Information