hexanoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】35921

【品名】hexanoyl chloride

【CA登记号】142-61-0

【分子式】C₆H₁₁ClO

【分子量】134.60544

【元素组成】C 53.54% H 8.24% Cl 26.34% O 11.89%

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：(VI)

The reaction of 4-methoxybenzylmagnesium bromide (I) with 1,3,4-trimethylpyridinium bromide (II) in ether, followed by a Diels-Alder condensation with ethyl acrylate (III) gives ethyl 3-(4-methoxybenzyl)-2,4,8-trimethyl-2-azabicyclo[2.2.2]oct-7-ene-6-carboxylate (IV), which is cyclized by means of HF yielding ethyl 1,2,3,4,4a,5,10,10a-octahydro-7-methoxy-1,4a,5-trimethyl-2,5-methanobenzo[g]quinoline-3-carboxylate (V). Acylation of (V) with hexanoyl chloride (VI) and butyllithium-diisopropylamine in THF affords the corresponding acyl derivative (VII), which is submitted to a reductive ring opening with formic acid in refluxing mesytilene giving 1,2,3,4,5,6-hexahydro-8-methoxy-3,6,11-trimethyl-11-(3-oxo-1-octyl)-2,6-methano-3-benzazocine (VIII). Finally, this compound is demethylated with 48% HBr and treated with methanesulfonic acid.

参考文献中间体

合成目标

【1】 Michne, W.F.; 11-Substituted hexahydro-2,6-methano-3-benzazocines. US 4255579 .
【2】 Lewis, T.R.; Rosenberg, F.J.; Michalec, S.J.; Pierson, A.K.; Michne, W.F.; 2,6-Methano-3-benzazocin-11beta-yl)alkalones. 1. Alkylalkalones: A new series of N-methyl derivatives with novel opiate activity profiles. J Med Chem 1979, 22, 10, 1158-63.
【3】 Castaner, J.; Serradell, M.N.; Tonazocine mesylate. Drugs Fut 1984, 9, 11, 844.

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)	35917	bromo(4-methoxybenzyl)magnesium		C₈H₉BrMgO	详情	详情
(II)	35918	1,3,4-trimethylpyridinium bromide		C₈H₁₂BrN	详情	详情
(III)	10164	ethyl acrylate	140-88-5	C₅H₈O₂	详情	详情
(IV)	35919	methyl 3-(4-methoxybenzyl)-2,4,8-trimethyl-2-azabicyclo[2.2.2]oct-7-ene-6-carboxylate		C₂₀H₂₇NO₃	详情	详情
(V)	35920	methyl (1S)-4-methoxy-1,10,14-trimethyl-10-azatetracyclo[9.3.1.0(2,7).0(9,14)]pentadeca-2,4,6-triene-12-carboxylate		C₂₀H₂₇NO₃	详情	详情
(VI)	35921	hexanoyl chloride	142-61-0	C₆H₁₁ClO	详情	详情
(VII)	35922	methyl (1S)-12-hexanoyl-4-methoxy-1,10,14-trimethyl-10-azatetracyclo[9.3.1.0(2,7).0(9,14)]pentadeca-2,4,6-triene-12-carboxylate		C₂₆H₃₇NO₄	详情	详情
(VIII)	35923	1-[(1S,9R)-4-methoxy-1,10,13-trimethyl-10-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-trien-13-yl]-3-octanone		C₂₄H₃₇NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The title compound was isolated from the cellular slime mold Dictyostelium purpureum K1001. A method for the total synthesis of this compound has also been reported. Oxidative dimerization of 1,3,5-trimethoxybenzene (I) to the biphenyl derivative (II) was accomplished by iodination with I2/HIO3, followed by Ullmann coupling in the presence of copper powder. Demethylation and cyclization of (II) with HI in HOAc led to the tetrahydroxy dibenzofuran (III). The 1 and 9 hydroxyl groups of (III) were then protected by formation of the cyclic silyl ether (IV). Subsequent methylation with iodomethane gave the desired dimethoxy derivative (V), which was then desilylated to (VI) by treatment with tetrabutylammonium fluoride. Esterification of (VI) with caproyl chloride (VII) in pyridine afforded (VIII). Caproate ester (VIII) was then subjected to a photo-induced Fries rearrangement producing ketone (IX). Finally, complete aromatic halogenation to furnish the title compound was carried out by means of benzyltrimethylammonium tetrachloroiodate.

参考文献中间体

合成目标

【1】 Aono, M.; Sawada, T.; Awano, K.; Ito, A.; Asakawa, S.; Structure determination and total synthesis of a novel antibacterial substance, AB0022A, produced by a cellular slime mold. J Antibiot 2000, 53, 9, 959.

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)	56555	1,3,5-Trimethoxybenzene; Phloroglucinol trimethyl ether	621-23-8	C₉H₁₂O₃	详情	详情
(II)	56556	2,2',4,4',6,6'-hexamethoxy-1,1'-biphenyl; methyl 2',4,4',6,6'-pentamethoxy[1,1'-biphenyl]-2-yl ether		C₁₈H₂₂O₆	详情	详情
(III)	56557	dibenzo[b,d]furan-1,3,7,9-tetrol		C₁₂H₈O₅	详情	详情
(IV)	56558	5,5-di(tert-butyl)[1]benzofuro[4,3,2-def][1,3,2]benzodioxasilepine-2,8-diol		C₂₀H₂₄O₅Si	详情	详情
(V)	56559	5,5-di(tert-butyl)-2,8-dimethoxy[1]benzofuro[4,3,2-def][1,3,2]benzodioxasilepine; 5,5-di(tert-butyl)-8-methoxy[1]benzofuro[4,3,2-def][1,3,2]benzodioxasilepin-2-yl methyl ether		C₂₂H₂₈O₅Si	详情	详情
(VI)	56560	3,7-dimethoxydibenzo[b,d]furan-1,9-diol		C₁₄H₁₂O₅	详情	详情
(VII)	35921	hexanoyl chloride	142-61-0	C₆H₁₁ClO	详情	详情
(VIII)	56561	9-hydroxy-3,7-dimethoxydibenzo[b,d]furan-1-yl hexanoate		C₂₀H₂₂O₆	详情	详情
(IX)	56562	1-(1,9-dihydroxy-3,7-dimethoxydibenzo[b,d]furan-2-yl)-1-hexanone		C₂₀H₂₂O₆	详情	详情

Extended Information