4-methyl-3-penten-2-one -Drug Synthesis Database

【结构式】

【分子编号】42266

【品名】4-methyl-3-penten-2-one

【CA登记号】141-79-7

【分子式】C₆H₁₀O

【分子量】98.1448

【元素组成】C 73.43% H 10.27% O 16.3%

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：(II)

Synthesis of aldehyde intermediate (IX): The condensation of 1-tert-butoxy-4-chlorobutane (I) with 4-methyl-3-penten-2-one (II) by means of Mg in hot THF gives the 2-octanone (III), which is condensed with hexafluoroacetone (IV) by means of diethyl chlorophosphate and LDA in THF to yield the fluorinated alkynol (V). Hydrogenation of the triple bond of (V) with H2 and Lindlar catalyst affords the cis-alkene (VI), which is deprotected with sulfuric acid to provide the fluorinated diol (VII). Finally, the primary alcohol of (VII) is oxidized to the corresponding aldehyde (VIII) with NaOCl and tempo, which is silylated with Tes-Cl and TEA to afford the desired intermediate (IX).

参考文献中间体

合成目标

【1】 Wirz, B.; Hilpert, H.; Novel versatile approach to an enantiopure 19-nor, des-C,D vitamin D-3 derivative. Tetrahedron 2001, 57, 4, 681.
【2】 Hilpert, H.; Wirz, B. (F. Hoffmann-La Roche AG); New process for the preparation of retiferol derivs.. EP 1094060 .

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)	49032	tert-butyl 4-chlorobutyl ether; 1-(tert-butoxy)-4-chlorobutane		C₈H₁₇ClO	详情	详情
(II)	42266	4-methyl-3-penten-2-one	141-79-7	C₆H₁₀O	详情	详情
(III)	49033	8-(tert-butoxy)-4,4-dimethyl-2-octanone		C₁₄H₂₈O₂	详情	详情
(IV)	44260	1,1,1,3,3,3-hexafluoroacetone	684-16-2	C₃F₆O	详情	详情
(V)	49034	10-(tert-butoxy)-1,1,1-trifluoro-6,6-dimethyl-2-(trifluoromethyl)-3-decyn-2-ol		C₁₇H₂₆F₆O₂	详情	详情
(VI)	49035	(Z)-10-(tert-butoxy)-1,1,1-trifluoro-6,6-dimethyl-2-(trifluoromethyl)-3-decen-2-ol		C₁₇H₂₈F₆O₂	详情	详情
(VII)	49036	(Z)-10,10,10-trifluoro-5,5-dimethyl-9-(trifluoromethyl)-7-decene-1,9-diol		C₁₃H₂₀F₆O₂	详情	详情
(VIII)	49037	(Z)-10,10,10-trifluoro-9-hydroxy-5,5-dimethyl-9-(trifluoromethyl)-7-decenal		C₁₃H₁₈F₆O₂	详情	详情
(IX)	49038	(Z)-10,10,10-trifluoro-5,5-dimethyl-9-[(triethylsilyl)oxy]-9-(trifluoromethyl)-7-decenal		C₁₉H₃₂F₆O₂Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Thiophenol (I) is treated with mesityl oxide (II) in CHCl3 and Et3N to yield derivative (III), which is then converted into alcohol (IV) by means of methylmagnesium iodide in Et2O. Cyclization of (IV) by means of AlCl3 in CS2 affords benzothiopyrane derivative (V) (1), which is nitrated by means of HNO3 and Ac2O or HOAc followed by treatment with Na2CO3 to provide (VI). Nitro derivative (VI) is then reduced with TiCl3 and HOAc or HCl and treated with NaOH to yield (VII). Amine (VII) is finally acylated with acid chloride (VIII) in benzene and pyridine.

参考文献中间体

合成目标

【1】 Spruce, L.W.; et al.; Novel heteroarotinoids: Synthesis and biological activity. J Med Chem 1991, 34, 1, 430.
【2】 Lu, S.; Zacheis, D.; Dhar, A.; et al.; Heteroarotinoids inhibit head and neck cancer cell lines in vitro and in vivo through both RAR and RXR retinoic acid receptors. J Med Chem 1999, 42, 21, 4434.
【3】 Nelson, E.C.; Madler, M.M.; Subramanian, S.; Birckbichler, P.J.; Berlin, K.D.; Patterson, M.K. Jr.; Benbrook, D.M. (Oklahoma State University); Heteroarotinoids - Anticancer agents with receptor specificity and TGASE activity. WO 9807716 .

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)	12951	Benzenethiol; Phenylmercaptan; Phenylhydrosulfide	108-98-5	C₆H₆S	详情	详情
(II)	42266	4-methyl-3-penten-2-one	141-79-7	C₆H₁₀O	详情	详情
(III)	42267	4-methyl-4-(phenylsulfanyl)-2-pentanone		C₁₂H₁₆OS	详情	详情
(IV)	42268	2,4-dimethyl-4-(phenylsulfanyl)-2-pentanol		C₁₃H₂₀OS	详情	详情
(V)	42269	2,2,4,4-tetramethylthiochromane		C₁₃H₁₈S	详情	详情
(VI)	42270	2,2,4,4-tetramethyl-6-nitrothiochromane		C₁₃H₁₇NO₂S	详情	详情
(VII)	42271	2,2,4,4-tetramethyl-6-thiochromanamine; 2,2,4,4-tetramethyl-3,4-dihydro-2H-thiochromen-6-ylamine		C₁₃H₁₉NS	详情	详情
(VIII)	42272	4-acetylbenzoyl chloride		C₉H₇ClO₂	详情	详情

Extended Information