(2S)-2-methoxy-2-methylpentanal -Drug Synthesis Database

【结构式】

【分子编号】55189

【品名】(2S)-2-methoxy-2-methylpentanal

【CA登记号】

【分子式】C₇H₁₄O₂

【分子量】130.18696

【元素组成】C 64.58% H 10.84% O 24.58%

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：(XLVI)

In a different procedure, reduction of methyl 2-methyl-2-pentenoate (XXXVIII) with LiAlH4 afforded the allylic alcohol (XXXIX). Sharpless asymmetric epoxidation of (XXXIX) provided the chiral epoxy alcohol (XL), which was subsequently esterified with benzoyl chloride, yielding the epoxy benzoate (XLI). Reduction of (XLI) with LiAlH4 furnished diol (XLII). After protection of the primary alcohol of (XLII) as the benzyl ether (XLIII), its tertiary hydroxyl group was alkylated with iodomethane to give the methoxy derivative (XLIV). Hydrogenolysis of the benzyl ether group of (XLIV) over Pearlman's catalyst, followed by oxidation of the resultant alcohol (XLV) with pyridinium chlorochromate, led to aldehyde (XLVI). This was condensed with p-toluenesulfinamide (XLVII) in the presence of titanium ethoxide producing the sulfinimide (XLVIII). Diastereoselective condensation of N-Boc-2-(tert-butyldimethylsilyloxy)pyrrole (XLIX) with the chiral sulfinimide (XLVIII) gave rise to the pyrrolidone adduct (L). Copper-catalyzed conjugate addition of propenylmagnesium bromide to the unsaturated lactam (L) provided the (Z)-propenyl pyrrolidinone (LI). Introduction of a cyano group to give (LII) was accomplished by lactam reduction with DIBAL followed by treatment with MeOH and PPTS and cyanide addition as above.

参考文献中间体

合成目标

【1】 Inhibitors of neuraminidases. WO 0128996 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXXVIII)	55181	Methyl trans-2-methyl-2-pentenoate	C₇H₁₂O₂	详情	详情
(XXXIX)	55182	2-Methyl-2-penten-1-ol	C₆H₁₂O	详情	详情
(XL)	55183	[(2R,3R)-3-ethyl-2-methyloxiranyl]methanol	C₆H₁₂O₂	详情	详情
(XLI)	55184	[(2R,3R)-3-ethyl-2-methyloxiranyl]methyl benzoate	C₁₃H₁₆O₃	详情	详情
(XLII)	55185	(2S)-2-methyl-1,2-pentanediol	C₆H₁₄O₂	详情	详情
(XLIII)	55186	(2S)-1-(benzyloxy)-2-methyl-2-pentanol	C₁₃H₂₀O₂	详情	详情
(XLIV)	55187	benzyl (2S)-2-methoxy-2-methylpentyl ether; 1-({[(2S)-2-methoxy-2-methylpentyl]oxy}methyl)benzene	C₁₄H₂₂O₂	详情	详情
(XLV)	55188	(2S)-2-methoxy-2-methyl-1-pentanol	C₇H₁₆O₂	详情	详情
(XLVI)	55189	(2S)-2-methoxy-2-methylpentanal	C₇H₁₄O₂	详情	详情
(XLVII)	55190	4-methylbenzenesulfinamide	C₇H₉NOS	详情	详情
(XLVIII)	55191	N-[(E,2S)-2-methoxy-2-methylpentylidene]-4-methylbenzenesulfinamide	C₁₄H₂₁NO₂S	详情	详情
(XLIX)	55192	tert-butyl 2-{[tert-butyl(dimethyl)silyl]oxy}-1H-pyrrole-1-carboxylate	C₁₅H₂₇NO₃Si	详情	详情
(L)	55193	tert-butyl (2R)-2-((1R,2S)-2-methoxy-2-methyl-1-{[(4-methylphenyl)sulfinyl]amino}pentyl)-5-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate	C₂₃H₃₄N₂O₅S	详情	详情
(LI)	55194	tert-butyl (2R,3S)-2-((1R,2S)-2-methoxy-2-methyl-1-{[(4-methylphenyl)sulfinyl]amino}pentyl)-5-oxo-3-[(Z)-1-propenyl]-1-pyrrolidinecarboxylate	C₂₆H₄₀N₂O₅S	详情	详情
(LII)	55195	tert-butyl (2R,3S,5R)-5-cyano-2-((1R,2S)-2-methoxy-2-methyl-1-{[(4-methylphenyl)sulfinyl]amino}pentyl)-3-[(Z)-1-propenyl]-1-pyrrolidinecarboxylate	C₂₇H₄₁N₃O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XLVI)

In a related procedure, aldehyde (XLVI) was condensed with triphenylmethanesulfenamide (LIV), producing the S-trityl sulfenimine (LV). Aldol-type condensation of (LV) with the silyloxy pyrrole (XLIX) gave rise to a diastereoisomeric mixture of adducts from which the desired isomer (LVI) was isolated as the major compound. Diastereoselectivity was increased using triflic acid as the condensation catalyst. Conjugate addition to (LVI) of propenylmagnesium bromide in the presence of CuBr yielded (LVII). Conversion of pyrrolidinone (LVII) to the cyano pyrrolidine (LVIII) was accomplished by the same sequence as above. Then, acidic cleavage of the tritylsulfanyl group of (LVIII), followed by N-acetylation, furnished the intermediate (XXXVII), which was finally processed as in the preceding methods.

参考文献中间体

合成目标

【1】 Barnes, D.M.; et al.; Synthesis of an influenza neuraminidase inhibitor intermediate via a highly diastereoselective coupling reaction. Org Lett 2002, 4, 9, 1427.
【2】 Inhibitors of neuraminidases. WO 0128996 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXXVII)	55180	tert-butyl (2R,3S,5R)-2-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-5-cyano-3-[(Z)-1-propenyl]-1-pyrrolidinecarboxylate	C₂₂H₃₇N₃O₄	详情	详情
(XLVI)	55189	(2S)-2-methoxy-2-methylpentanal	C₇H₁₄O₂	详情	详情
(XLIX)	55192	tert-butyl 2-{[tert-butyl(dimethyl)silyl]oxy}-1H-pyrrole-1-carboxylate	C₁₅H₂₇NO₃Si	详情	详情
(LIV)	55197	Triphenylmethanesulfenamide	C₁₉H₁₇NS	详情	详情
(LV)	55198	N-[(E,2S)-2-methoxy-2-methylpentylidene](triphenyl)methanesulfenamide	C₂₆H₂₉NOS	详情	详情
(LVI)	55199	tert-butyl (2R)-2-{(1R,2S)-2-methoxy-2-methyl-1-[(tritylsulfanyl)amino]pentyl}-5-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate	C₃₅H₄₂N₂O₄S	详情	详情
(LVII)	55200	tert-butyl (2R,3S)-2-{(1R,2S)-2-methoxy-2-methyl-1-[(tritylsulfanyl)amino]pentyl}-5-oxo-3-[(Z)-1-propenyl]-1-pyrrolidinecarboxylate	C₃₈H₄₈N₂O₄S	详情	详情
(LVIII)	55201	tert-butyl (2R,3S,5R)-5-cyano-2-{(1R,2S)-2-methoxy-2-methyl-1-[(tritylsulfanyl)amino]pentyl}-3-[(Z)-1-propenyl]-1-pyrrolidinecarboxylate	C₃₉H₄₉N₃O₃S	详情	详情

Extended Information