ethyl 4-sulfanylphenylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】13295

【品名】ethyl 4-sulfanylphenylcarbamate

【CA登记号】

【分子式】C₉H₁₁NO₂S

【分子量】197.25788

【元素组成】C 54.8% H 5.62% N 7.1% O 16.22% S 16.26%

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)

The acylation of 4-aminothiophenol (I) with ethyl chloroformate (II) is performed in a nitrogen atmosphere in the presence of NaHCO3 in CH2Cl2 / water medium giving ethyl (4-mercaptophenyl)carbamate (III). This compound is condensed with cis-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dixolan-4-yl]methyl methanesulfonate (IV) in the presence of K2CO3 in refluxing acetone under nitrogen, affording the title compound, which is converted to the monohydrochloride with i-PrOH / HCl in 4-methyl-2-pentanone.

参考文献中间体

合成目标

【1】 Heeres, J.; Van der Veken, L.J.E.; Novel (2-aryl-4-phenylthioalkyl-1,3-dioxolan-2-yl-methyl)azole derivatives. DE 3166517D; EP 0052905 .
【2】 Van Ginckel, R.; Geuens, G.; Heeres, J.; Tubulozole Hydrochloride. Drugs Fut 1984, 9, 12, 911.

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)	16490	4-aminophenylhydrosulfide; 4-aminothiophenol; 4-aminobenzenethiol	1193-02-8	C₆H₇NS	详情	详情
(II)	11229	1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate	541-41-3	C₃H₅ClO₂	详情	详情
(III)	13295	ethyl 4-sulfanylphenylcarbamate		C₉H₁₁NO₂S	详情	详情
(IV)	34328	1-[[(2S,4S)-2-(2,4-dichlorophenyl)-4-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-1,3-dioxolan-2-yl]methyl]-1H-imidazole		C₁₇H₂₀Cl₂N₂O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The synthesis of erbulozole, starting from 1-(4-methoxyphenyl)-2-(1H-imidazol-1-yl)ethanone (I) is outlined. Ketalization of (I) with glycerin (II) was performed in n-heptane with p-toluenesulfonic acid as the catalyst and under azeotropic removal of H2O. The resulting dioxolane derivative (III), arising as a cis-trans mixture, was benzoylated to the ester (IV). Cis-trans isomers were separated by column chromatography over silica gel (Merck, Silica gel 60), using a mixture of trichloromethane and methanol (98:2 by volume) as the eluent. Saponification of the cis-benzoate (V) with sodium hydroxide in dioxane-water medium at room temperature afforded the alcohol (VI), which was converted to the methanesulfonate (VII) with methanesulfonylchloride in dry pyridine and methylenechloride (1:1 by volume). Under a nitrogen atmosphere, compound (VII) was coupled with (VIII) in acetone using K2CO3 as an acid acceptor to the target compound, erbulozole.

参考文献中间体

合成目标

【1】 Van Ginckel, R.; Geuens, G.; Heeres, J.; Tubulozole Hydrochloride. Drugs Fut 1984, 9, 12, 911.
【2】 Distelmans, R.; Van Ginckel, R.; Van Der Veken, L.J.E.; Heeres, J.; Erbulozole. Drugs Fut 1991, 16, 6, 507.

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)	13288	2-(1H-Imidazol-1-yl)-1-(4-methoxyphenyl)-1-ethanone		C₁₂H₁₂N₂O₂	详情	详情
(II)	13289	Glycerine; Glycerin; Glycerol	56-81-5	C₃H₈O₃	详情	详情
(III)	13290	[2-(1H-Imidazol-1-ylmethyl)-2-(4-methoxyphenyl)-1,3-dioxolan-4-yl]methanol		C₁₅H₁₈N₂O₄	详情	详情
(IV)	13291	[2-(1H-imidazol-1-ylmethyl)-2-(4-methoxyphenyl)-1,3-dioxolan-4-yl]methyl benzoate		C₂₂H₂₂N₂O₅	详情	详情
(V)	13292	[(2R,4R)-2-(1H-imidazol-1-ylmethyl)-2-(4-methoxyphenyl)-1,3-dioxolan-4-yl]methyl benzoate		C₂₂H₂₂N₂O₅	详情	详情
(VI)	13293	[(2R,4S)-2-(1H-Imidazol-1-ylmethyl)-2-(4-methoxyphenyl)-1,3-dioxolan-4-yl]methanol		C₁₅H₁₈N₂O₄	详情	详情
(VII)	13294	[(2R,4R)-2-(1H-imidazol-1-ylmethyl)-2-(4-methoxyphenyl)-1,3-dioxolan-4-yl]methyl methanesulfonate		C₁₆H₂₀N₂O₆S	详情	详情
(VIII)	13295	ethyl 4-sulfanylphenylcarbamate		C₉H₁₁NO₂S	详情	详情

Extended Information