ethyl 7-bromoheptanoate -Drug Synthesis Database

【结构式】

【分子编号】36428

【品名】ethyl 7-bromoheptanoate

【CA登记号】29823-18-5

【分子式】C₉H₁₇BrO₂

【分子量】237.13678

【元素组成】C 45.59% H 7.23% Br 33.7% O 13.49%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The condensation of diethyl acetamidomalonate (I) with ethyl 7-bromoheptanoate (II) by means of sodium ethoxide in refluxing ethanol gives diethyl acetamido-(6-ethoxycarbonylhexyl)malonate (III), which is hydrolyzed and decarboxylated with refluxing concentrated HCl yielding 2-aminononanedioic acid (IV). This acid is esterified with SOCl2 and ethanol to the corresponding diethyl ester (V), which is condensed with vinyl cyclohexyl ketone (VI) to afford diethyl 2-[(3-oxo-3-cyclohexylpropyl)amino]nonanedioate (VII). The reaction of (VII) with potassium cyanate in ethanol-HCl gives the corresponding hydantoic ester (VIII), which is cyclized by heating at 100 C affording 5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-oxopropyl)hydantoin (IX). Finally, this compound is reduced with NaBH4 in ethanol.

参考文献中间体

合成目标

【1】 Whittaker, N.; Harris, C.J.; Stepney, R.; Caldwell, A.G.; Heterocyclic prostaglandin analogs. Part 2. Hydantoins and other imidazole analogs. J Chem Soc - Perkins Trans I 1980, 1, 2, 495-505.
【2】 Harris, C.J.; Stepney, R.; Caldwell, A.G.; Whittaker, N.; Hydantoin prostaglandin analog, potemt and selective inhibitors of platelet aggregation. J Chem Soc Chem Commun 1979, 13, 561-562.
【3】 Caldwell, A.G.; Whittaker, N.; US 4204068 .
【4】 Caldwell, A.G.; Whittaker, N.; BE 0876670 .
【5】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Hillier, K.; BW-245-C. Drugs Fut 1982, 7, 6, 380.

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)	16710	Diethyl 2-(acetamido)malonate; Diethyl acetamidomalonate	1068-90-2	C₉H₁₅NO₅	详情	详情
(II)	36428	ethyl 7-bromoheptanoate	29823-18-5	C₉H₁₇BrO₂	详情	详情
(III)	36429	triethyl 1-(acetamido)-1,1,7-heptanetricarboxylate		C₁₈H₃₁NO₇	详情	详情
(IV)	36430	2-aminononanedioic acid		C₉H₁₇NO₄	详情	详情
(V)	36431	diethyl 2-aminononanedioate		C₁₃H₂₅NO₄	详情	详情
(VI)	36432	1-cyclohexyl-2-propen-1-one		C₉H₁₄O	详情	详情
(VII)	36433	diethyl 2-[(3-cyclohexyl-3-oxopropyl)amino]nonanedioate		C₂₂H₃₉NO₅	详情	详情
(VIII)	36434	diethyl 2-[(aminocarbonyl)(3-cyclohexyl-3-oxopropyl)amino]nonanedioate		C₂₃H₄₀N₂O₆	详情	详情
(IX)	36435	7-[3-(3-cyclohexyl-3-oxopropyl)-2,5-dioxo-4-imidazolidinyl]heptanoic acid		C₁₉H₃₀N₂O₅	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 reaction of ethyl 7-bromoheptanoate (I) with NaI, Zn, dibromoethane, LiCl and CuCN gives the organometallic derivative (II), which is condensed with 4-bromobenzoyl chloride (III) in THF to yield 8-(4-bromophenyl)-8-oxooctanoic acid ethyl ester (IV). The condensation of (IV) with 4-bromophenylboronic acid (V) by means of Pd(PPh3)4 and K2CO3 in hot toluene affords 8-(4'-bromobiphenyl-4-yl)-8-oxooctanoic acid ethyl ester (VI), which is hydrolyzed with NaOH in THF/methanol to provide the corresponding carboxylic acid (VII). Finally, this compound is treated with hydroxylamine, EDC, HOBt and TEA to obtain the target hydroxamic acid.

参考文献中间体

合成目标

【1】 Woo, S.H.; et al.; Structurally simple trichostatin A-like straight chain hydroxamates as potent histone deacetylase inhibitors. J Med Chem 2002, 45, 13, 2877.
【2】 Delorme, D.; Woo, S.H.; Vaisburg, A. (MethylGene Inc.); Inhibitors of histone deacetylase. WO 0170675 .

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)	36428	ethyl 7-bromoheptanoate	29823-18-5	C₉H₁₇BrO₂	详情	详情
(II)	55802			C₁₀H₁₇CuINO₂Zn	详情	详情
(III)	45960	4-bromobenzoyl chloride	586-75-4	C₇H₄BrClO	详情	详情
(IV)	55803	ethyl 8-(4-bromophenyl)-8-oxooctanoate		C₁₆H₂₁BrO₃	详情	详情
(V)	55804	4-Bromobenzeneboronic acid; 4-Bromophenylboronic acid	5467-74-3	C₆H₆BBrO₂	详情	详情
(VI)	55805	ethyl 8-(4'-bromo[1,1'-biphenyl]-4-yl)-8-oxooctanoate		C₂₂H₂₅BrO₃	详情	详情
(VII)	55806	8-(4'-bromo[1,1'-biphenyl]-4-yl)-8-oxooctanoic acid		C₂₀H₂₁BrO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Alkylation of (R)-5-(t-butyldimethylsilyloxymethyl)pyrrolidin-2-one (I) with ethyl 7-bromoheptanoate (II) affords the pyrrolidone-ester (III). After removal of the silyl protecting group of (III) with tetrabutylammonium fluoride, the resultant alcohol (IV) is oxidized to aldehyde (V) under modified Swern conditions, using DMSO/EDC

参考文献中间体

合成目标

【1】 Cameron, K.O.; Crawford, D.T.; DaSilva-Jardine, P.; et al.; Discovery and bone anabolic activity of highly selective EP4 receptor prostaglandin E2 (PGE2) agonists. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 307.
【2】 Thompson, D.D.; Lefker, B.A.; Cameron, K.O.; Ke, H.Z. (Pfizer Products Inc.); EP4 receptor selective agonists in the treatment of osteoporosis. EP 1110949; JP 2001181210; WO 0146140 .

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)	60581	(5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-pyrrolidinone		C₁₁H₂₃NO₂Si	详情	详情
(II)	36428	ethyl 7-bromoheptanoate	29823-18-5	C₉H₁₇BrO₂	详情	详情
(III)	60582	ethyl 7-[(2R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-oxopyrrolidinyl]heptanoate		C₂₀H₃₉NO₄Si	详情	详情
(IV)	60583	ethyl 7-[(2R)-2-(hydroxymethyl)-5-oxopyrrolidinyl]heptanoate		C₁₄H₂₅NO₄	详情	详情
(V)	60584	ethyl 7-[(2R)-2-formyl-5-oxopyrrolidinyl]heptanoate		C₁₄H₂₃NO₄	详情	详情

Extended Information