tert-butyl hydroperoxide -Drug Synthesis Database

【结构式】

【分子编号】37518

【品名】tert-butyl hydroperoxide

【CA登记号】75-91-2

【分子式】C₄H₁₀O₂

【分子量】90.1222

【元素组成】C 53.31% H 11.18% O 35.51%

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：(E)

The controlled epoxidation of 1,3-cyclooctadiene (XXI) gives the monoepoxide (XXII), which by isomerization is converted into the bicyclic alcohol (XXIII). The epoxidation of (XXIII) with tert-butyl hydroperoxide (E) and vanadyl acetylacetonate in refluxing benzene gives the epoxide (XXIV), which is protected with tert-butyldimethylsilyl chloride yielding the corresponding silylether (XXV). The reaction of (XXV) with 1,3-bis(methylthio)allyllithium (XXVI) in THF gives the condensation product (XXVII), which by treatment with HgCl2 and CaCO3 affords the hydroxyaldehyde (XXVIII). The reaction of (XXVIII) with n-amyllithium (F) in THF yields the diol (XXIX), which is protected with dihydropyran giving the bistetrahydropyranyl derivative (XXX). Elimination of the silyl group of (XXX) with tetrabutylammonium fluoride gives rise to the monohydroxybis(tetrahydropyranyl) derivative (XXXI), which is mesylated with methanesulfonyl chloride to the corresponding mesylate (XXXII). The treatment of (XXXII) with KOH in refluxing ethanol yields the diene (XXXIII), which is selectively epoxidized with m-chloroperbenzoic acid to the epoxide (XXXIV).

参考文献中间体

合成目标

【1】 Shibasaki, M.; Ikegami, S.; Ueda, J.; New synthetic routes to 9(O)-methanopostacyclin. A highly stable and biologically potent analog of prostacyclin. Tetrahedron Lett 1979, 5, 433-436.
【2】 Castaner, J.; Hillier, K.; Carbacyclin. Drugs Fut 1981, 6, 12, 753.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(E)	37518	tert-butyl hydroperoxide	75-91-2	C₄H₁₀O₂	详情	详情
(F)	37524	pentyllithium		C₅H₁₁Li	详情	详情
(XXI)	37515	1,3-Cyclooctadiene	3806-59-5	C₈H₁₂	详情	详情
(XXII)	37516	9-oxabicyclo[6.1.0]non-2-ene		C₈H₁₂O	详情	详情
(XXIII)	37517	(1R,3aS,6aS)-1,2,3,3a,4,6a-hexahydro-1-pentalenol		C₈H₁₂O	详情	详情
(XXIV)	37519	(1aS,1bR,2R,4aS,5aR)octahydropentaleno[1,2-b]oxiren-2-ol		C₈H₁₂O₂	详情	详情
(XXV)	37520	(1aS,1bS,2R,4aS,5aR)octahydropentaleno[1,2-b]oxiren-2-yl tert-butyl(dimethyl)silyl ether; [(1aS,1bS,2R,4aS,5aR)octahydropentaleno[1,2-b]oxiren-2-yloxy](tert-butyl)dimethylsilane		C₁₄H₂₆O₂Si	详情	详情
(XXVI)	37521	[(E)-1,3-bis(methylsulfanyl)-2-propenyl]lithium		C₅H₉LiS₂	详情	详情
(XXVII)	37522	(1R,2R,3aS,6R,6aS)-1-[(1R,2E)-1,3-bis(methylsulfanyl)-2-propenyl]-6-[[tert-butyl(dimethyl)silyl]oxy]octahydro-2-pentalenol		C₁₉H₃₆O₂S₂Si	详情	详情
(XXVIII)	37523	(E)-3-((1R,2R,3aS,6R,6aS)-6-[[tert-butyl(dimethyl)silyl]oxy]-2-hydroxyoctahydro-1-pentalenyl)-2-propenal		C₁₇H₃₀O₃Si	详情	详情
(XXIX)	37525	(1R,2R,3aS,6R,6aS)-6-[[tert-butyl(dimethyl)silyl]oxy]-1-[(E,3S)-3-hydroxy-1-octenyl]octahydro-2-pentalenol		C₂₂H₄₂O₃Si	详情	详情
(XXX)	37526	(2S,3E)-4-[(1S,2R,3aS,6R,6aS)-6-[[tert-butyl(dimethyl)silyl]oxy]-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]octahydro-1-pentalenyl]-2-pentyl-3-butenyl tetrahydro-2H-pyran-2-yl ether; [((1R,3aS,5R,6S,6aS)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-6-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]octahydro-1-pentalenyl)oxy](tert-butyl)dimethylsilane		C₃₄H₆₂O₅Si	详情	详情
(XXXI)	37527	(1R,3aS,5R,6S,6aS)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-6-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]octahydro-1-pentalenol		C₂₈H₄₈O₅	详情	详情
(XXXII)	37528	2-[((2S,3E)-4-[(1S,2R,3aS,6R,6aS)-6-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]octahydro-1-pentalenyl]-2-pentyl-3-butenyl)oxy]tetrahydro-2H-pyran; (2S,3E)-4-[(1S,2R,3aS,6R,6aS)-6-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]octahydro-1-pentalenyl]-2-pentyl-3-butenyl tetrahydro-2H-pyran-2-yl ether		C₃₁H₅₄O₅S	详情	详情
(XXXIII)	37529	2-[((1S,2R,3aS,6aR)-1-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]-1,2,3,3a,4,6a-hexahydro-2-pentalenyl)methoxy]tetrahydro-2H-pyran; (2S,3E)-4-[(1S,2R,3aS,6aR)-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1,2,3,3a,4,6a-hexahydro-1-pentalenyl]-2-pentyl-3-butenyl tetrahydro-2H-pyran-2-yl ether		C₂₈H₄₆O₄	详情	详情
(XXXIV)	37530	(1aS,1bS,2S,3R,4aR)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]octahydropentaleno[1,2-b]oxirene; (2S,3E)-4-[(1aS,1bS,2S,3R,4aR)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]octahydropentaleno[1,2-b]oxiren-2-yl]-2-pentyl-3-butenyl tetrahydro-2H-pyran-2-yl ether		C₂₈H₄₆O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The chlorination of 2,3-dimethyl-4-(2,2,2-trifluoroethoxy)pyridine-N-oxide (I) with trichloroisocyanuric acid in hot chloroform gives the 2-chloromethyl derivative (II), which is condensed with 2-mercapto-1H-benzimidazole (III) by means of NaOH in methanol to yield the adduct (IV). The reaction of (IV) with PCl3 and acetic acid eliminates the N-oxide group, affording the sulfanylmethylpyridine (V). Finally, this compound is oxidized with tert-butyl hydroperoxide (VI) in ethanol to provide the target sulfoxide. Alternatively, the intermediate adduct (IV) can also be obtained as follows: The chlorination of 2,3-dimethyl-4-nitropyridine-N-oxide (VII) with trichloroisocyanuric acid as before gives the chloromethyl derivative (VIII), which is condensed with 2-mercapto-1H-benzimidazole (III) as before to yield the adduct (IX). Finally, this compound is treated with 2,2,2-trifluoroethanol (X), benzyltrimethylammonium chloride and K2CO3 in acetonitrile to afford the target intermediate (IV).

参考文献中间体

合成目标

【1】 Montserrat Vidal, C.; Serra Macia, X. (Laboratorios Salvat SA); Intermediate for the synthesis of lansoprazole and process for obtaining it. ES 2063705 .

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)	19484	2,3-dimethyl-4-(2,2,2-trifluoroethoxy)-1-pyridiniumolate		C₉H₁₀F₃NO₂	详情	详情
(II)	51411	2-(chloromethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)-1-pyridiniumolate		C₉H₉ClF₃NO₂	详情	详情
(III)	12821	2-Mercaptobenzinidiazole; 1H-Benzimidazol-2-ylhydrosulfide; 1H-Benzimidazole-2-thiol; 2-Benzimidazolethiol; o-Phenylenethiourea; 2-Benzimidazolinethione; 1,3-Dihydro-2H-benzimidazole-2-thione	583-39-1	C₇H₆N₂S	详情	详情
(IV)	51412	2-[(1H-benzimidazol-2-ylsulfanyl)methyl]-3-methyl-4-(2,2,2-trifluoroethoxy)-1-pyridiniumolate		C₁₆H₁₄F₃N₃O₂S	详情	详情
(V)	19488	2-[(1H-benzimidazol-2-ylsulfanyl)methyl]-3-methyl-4-pyridinyl 2,2,2-trifluoroethyl ether; 2-([[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfanyl)-1H-benzimidazole	103577-40-8	C₁₆H₁₄F₃N₃OS	详情	详情
(VI)	37518	tert-butyl hydroperoxide	75-91-2	C₄H₁₀O₂	详情	详情
(VII)	19482	2,3-dimethyl-4-nitro-1-pyridiniumolate	37699-43-7	C₇H₈N₂O₃	详情	详情
(VIII)	51413	2-(chloromethyl)-3-methyl-4-nitro-1-pyridiniumolate		C₇H₇ClN₂O₃	详情	详情
(IX)	51414	2-[(1H-benzimidazol-2-ylsulfanyl)methyl]-3-methyl-4-nitro-1-pyridiniumolate		C₁₄H₁₂N₄O₃S	详情	详情
(X)	19483	2,2,2-trifluoro-1-ethanol	75-89-8	C₂H₃F₃O	详情	详情

Extended Information