5-[4-hydroxy-2-(3-hydroxybutyl)-3,5,6-trimethylphenoxy]-2,2-dimethylpentanoic acid -Drug Synthesis Database

【结构式】

【分子编号】23823

【品名】5-[4-hydroxy-2-(3-hydroxybutyl)-3,5,6-trimethylphenoxy]-2,2-dimethylpentanoic acid

【CA登记号】

【分子式】C₂₀H₃₂O₅

【分子量】352.47108

【元素组成】C 68.15% H 9.15% O 22.7%

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：(V)

Arylbutanone (I), which was in equilibrium with its hemiacetal cyclic form, was alkylated with isopropyl 5-bromo-2,2-dimethyl-pentanoate (II) in the presence of NaH to afford ether (III). After saponification of the isopropyl and acetate esters of (III) with ethanolic KOH, the resulting ketoacid (IV) was reduced with NaBH4 to yield hydroxyacid (V). Finally, cyclization of (V) using 2,2'-dipyridyl disulfide, triphenylphosphine and silver perchlorate produced the target macrocyclic lactone.

参考文献中间体

合成目标

【1】 Baldazzi, C.; et al.; Medium sized lactones with hyplipidaemic and antio. Bioorg Med Chem 1999, 7, 2, 411.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	23819	4-hydroxy-2,3,6-trimethyl-5-(3-oxobutyl)phenyl acetate	C₁₅H₂₀O₄	详情	详情
(II)	23820	isopropyl 5-bromo-2,2-dimethylpentanoate	C₁₀H₁₉BrO₂	详情	详情
(III)	23821	isopropyl 5-[4-(acetoxy)-2,3,5-trimethyl-6-(3-oxobutyl)phenoxy]-2,2-dimethylpentanoate	C₂₅H₃₈O₆	详情	详情
(IV)	23822	5-[4-hydroxy-2,3,5-trimethyl-6-(3-oxobutyl)phenoxy]-2,2-dimethylpentanoic acid	C₂₀H₃₀O₅	详情	详情
(V)	23823	5-[4-hydroxy-2-(3-hydroxybutyl)-3,5,6-trimethylphenoxy]-2,2-dimethylpentanoic acid	C₂₀H₃₂O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

In an alternative procedure, isovanillin (XI) was protected by O-benzylation, giving (XII), and its aldehyde group was subsequently reduced to alcohol (XIII) with NaBH4. The benzylic alcohol (XIII) was chlorinated to (XIV), which was converted to nitrile (XV) by chloride displacement with tetraethylammonium cyanide. Nitrile (XV) was subjected to Claisen condensation with ethyl formate, yielding (XVI), followed by sulfonylation with benzenesulfonyl chloride to afford (XVII), which was cyclized to the amino thiophene (XVIII) by treatment with ethyl thioglycolate (IV) as above. Condensation of (XVIII) with 2,5-dimethoxytetrahydrofuran (VI) produced the corresponding pyrrole derivative (XIX). After conversion of the ester group of (XIX) to amide (XX) upon heating with pyrrolidine (VIII), its cyclization with POCl3 furnished the thienopyrrolizinone (XXI). The O-benzyl protecting group of (XXI) was finally cleaved by treatment with HBr in HOAc.

参考文献中间体

合成目标

【1】 Lisowski, V.; et al.; Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents. Bioorg Med Chem Lett 2001, 11, 16, 2205.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	18838	methyl 2-sulfanylacetate	2365-48-2	C₃H₆O₂S	详情	详情
(VI)	12121	(Z)-4-(Dimethylamino)-3-imidazo[1,2-a]pyridin-6-yl-3-buten-2-one		C₁₃H₁₅N₃O	详情	详情
(VIII)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(XI)	18455	3-hydroxy-4-methoxybenzaldehyde; Isovanillin	621-59-0	C₈H₈O₃	详情	详情
(XII)	10966	3-(Benzyloxy)-4-methoxybenzaldehyde; 3-Benzyloxy-4-methoxybenzaldehyde	6346-05-0	C₁₅H₁₄O₃	详情	详情
(XIII)	23823	5-[4-hydroxy-2-(3-hydroxybutyl)-3,5,6-trimethylphenoxy]-2,2-dimethylpentanoic acid		C₂₀H₃₂O₅	详情	详情
(XIV)	52232	benzyl 5-(chloromethyl)-2-methoxyphenyl ether; 2-(benzyloxy)-4-(chloromethyl)-1-methoxybenzene		C₁₅H₁₅ClO₂	详情	详情
(XV)	52233	(3-Benzyloxy-4-methoxyphenyl)acetonitrile		C₁₆H₁₅NO₂	详情	详情
(XVI)	52234	sodium (Z)-2-[3-(benzyloxy)-4-methoxyphenyl]-2-cyano-1-ethenolate		C₁₇H₁₄NNaO₃	详情	详情
(XVII)	52235	(Z)-2-[3-(benzyloxy)-4-methoxyphenyl]-2-cyanoethenyl benzenesulfonate		C₂₃H₁₉NO₅S	详情	详情
(XVIII)	52236	methyl 3-amino-4-[3-(benzyloxy)-4-methoxyphenyl]-2-thiophenecarboxylate		C₂₀H₁₉NO₄S	详情	详情
(XIX)	52234	sodium (Z)-2-[3-(benzyloxy)-4-methoxyphenyl]-2-cyano-1-ethenolate		C₁₇H₁₄NNaO₃	详情	详情
(XX)	52238	[4-[3-(benzyloxy)-4-methoxyphenyl]-3-(1H-pyrrol-1-yl)-2-thienyl](1-pyrrolidinyl)methanone		C₂₇H₂₆N₂O₃S	详情	详情
(XXI)	52239	3-[3-(benzyloxy)-4-methoxyphenyl]-8H-thieno[2,3-b]pyrrolizin-8-one		C₂₃H₁₇NO₃S	详情	详情

Extended Information