6-bromo-1-hexene -Drug Synthesis Database

【结构式】

【分子编号】37330

【品名】6-bromo-1-hexene

【CA登记号】2695-47-8

【分子式】C₆H₁₁Br

【分子量】163.05734

【元素组成】C 44.2% H 6.8% Br 49%

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)

Nalpha-Boc-Ngamma-tosyl-L-arginine (I) was converted to the N,O-dimethyl hydroxamate (II) by treatment with dimethylhydroxylamine and BOP. Condensation of (II) with the Grignard reagent (IV), prepared from 6-bromo-1-hexene (III), produced ketone (V). Then, oxidative cleavage of the terminal alkene of (V) by means of NaIO4 and RuCl3 yielded carboxylic acid (VI).

参考文献中间体

合成目标

【1】 DiMaio, J. (National Research Council of Canada); Thrombin inhibitors based on the amino acid sequence of hirudin. JP 1999502203; WO 9629347 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	13361	(Methoxyamino)methane; N,O-Dimethylhydroxylamine	1117-97-1	C₂H₇NO	详情	详情
(I)	19064	(2S)-2-[(tert-butoxycarbonyl)amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₁₈H₂₈N₄O₆S	详情	详情
(II)	37329	tert-butyl (1S)-4-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]-1-[[methoxy(methyl)amino]carbonyl]butylcarbamate		C₂₀H₃₃N₅O₆S	详情	详情
(III)	37330	6-bromo-1-hexene	2695-47-8	C₆H₁₁Br	详情	详情
(IV)	37331	bromo(5-hexenyl)magnesium		C₆H₁₁BrMg	详情	详情
(V)	37332	tert-butyl (1S)-1-[3-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]propyl]-2-oxo-7-octenylcarbamate		C₂₄H₃₈N₄O₅S	详情	详情
(VI)	37333	(7S)-7-[(tert-butoxycarbonyl)amino]-10-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]-6-oxodecanoic acid		C₂₃H₃₆N₄O₇S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIV)

Alkylation of the lithio-dianion of propargyl alcohol (XIII) with 6-bromo-1-hexene (XIV), followed by in situ reduction of the resultant disubstituted acetylene with lithium metal gave the allylic alcohol (XV). Asymmetric Sharpless epoxidation of (XV) using tert-butyl hydroperoxide in the presence of L-(+)-diisopropyl tartrate afforded the (S,S)-epoxy alcohol (XVI). This was reduced to the chiral diol (XVII) employing Red-Al® in THF. After formation of the bis-mesylate (XVIII), oxidative cleavage of the terminal double bond by means of NaIO4 in the presence of ruthenium catalyst furnished the carboxylic acid (XIX). The mesylate groups were finally displaced by sodium disulfide to produce the desired cyclic disulfide compound.

参考文献中间体

合成目标

【1】 Page, P.C.B.; et al.; An enantioselective synthesis of R-(+)-alpha-lipoic acid. J Chem Soc - Perkins Trans I 1990, 6, 1615.
【2】 Bulman, P.C.; et al.; Enantioselective synthesis of R-(+)-alpha-lipoic acid. J Chem Soc Chem Commun 1986, 18, 1408.
【3】 Sutherland, I.O.; Page, P.C.B.; Rayner, C.M. (Asta Medica AG); Process for the preparation of pure enantiomers of R-(+)-alpha-lipoic acid and S-(-)-alpha-lipoic acid (thioctic acid), and nonene or mesyl derivs. as intermediates thereof. DE 3629116; EP 0261336 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIII)	16664	Propargyl Alcohol; 2-propyn-1-ol	107-19-7	C₃H₄O	详情	详情
(XIV)	37330	6-bromo-1-hexene	2695-47-8	C₆H₁₁Br	详情	详情
(XV)	57945	(2E)-2,8-nonadien-1-ol		C₉H₁₆O	详情	详情
(XVI)	57946	[(2R,3S)-3-(5-hexenyl)oxiranyl]methanol		C₉H₁₆O₂	详情	详情
(XVII)	57947	(3S)-8-nonene-1,3-diol		C₉H₁₈O₂	详情	详情
(XVIII)	57948	(3S)-3-[(methylsulfonyl)oxy]-8-nonenyl methanesulfonate		C₁₁H₂₂O₆S₂	详情	详情
(XIX)	57949	(6S)-6,8-bis[(methylsulfonyl)oxy]octanoic acid		C₁₀H₂₀O₈S₂	详情	详情

Extended Information