1,1,1-trichloro-3-(4-methoxyphenyl)-2-propanimine -Drug Synthesis Database

【结构式】

【分子编号】63307

【品名】1,1,1-trichloro-3-(4-methoxyphenyl)-2-propanimine

【CA登记号】

【分子式】C₁₀H₁₀Cl₃NO

【分子量】266.55364

【元素组成】C 45.06% H 3.78% Cl 39.9% N 5.25% O 6%

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：

The synthesis of the C22-C34 subunit (C12-C16 of the chemical name) of FK-506 has been reported: The condensation of the chiral aldehyde (I) with the (S)-allenyl stannane (II) by means of boron trifluoride ethearate in dichloromethane yields an epimeric mixture of the acetylenic alcohol (III), which by protection with p-methoxybenzyl (PMB) trichloroacetimidate, followed by chromatographic separation, gives the enantiomerically pure protected acetylenic diol (IV). The reduction of (IV) with bis(2-methoxyethoxy)aluminum hydride in THF affords the (E,E)-dienic alcohol (V), which is submitted to a Sharpless asymmetric epoxidation with (-)-diethyl tartrate [(-)-DETR], titanium tetraisopropoxide and tert-butyl hydroperoxide (TBHP) in dichloromethane, yielding the chiral epoxy alcohol (VI). The reduction of (VI) with bis(2-methoxyethoxy)aluminum hydride in THF affords the partially protected triol (VII), which is finally dehydrogenated with dichlorodicyanobenzoquinone (DDQ) in dichloromethane to give the chiral 1,3-dioxane (VIII), which is the desired intermediate.

参考文献中间体

合成目标

【1】 Marshall, J.A.; Xie, S.P.; Synthesis of a C22-34 subunit of the immunosuppressant FK-506. J Org Chem 1995, 60, 22, 7230.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	63307	1,1,1-trichloro-3-(4-methoxyphenyl)-2-propanimine	C₁₀H₁₀Cl₃NO	详情	详情
(I)	11534	(E)-3-[(1R,3R,4R)-3-Methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-2-methyl-2-propenal	C₂₀H₃₈O₃Si	详情	详情
(II)	11569	2-(tributylstannyl)-2,3-pentadienyl pivalate	C₂₂H₄₂O₂Sn	详情	详情
(III)	11570	(4R,6E)-5-hydroxy-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-6-hepten-2-ynyl pivalate	C₃₀H₅₄O₅Si	详情	详情
(IV)	11571	(4R,5S,6E)-5-[(4-methoxybenzyl)oxy]-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-6-hepten-2-ynyl pivalate	C₃₈H₆₂O₆Si	详情	详情
(V)	11572	(2E,4R,5S,6E)-5-[(4-Methoxybenzyl)oxy]-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-2,6-heptadien-1-ol	C₃₃H₅₆O₅Si	详情	详情
(VI)	11573	[(2R,3R)-3-((1S,2S,3E)-2-[(4-Methoxybenzyl)oxy]-4-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1,3-dimethyl-3-butenyl)oxiranyl]methanol	C₃₃H₅₆O₆Si	详情	详情
(VII)	11574	(3S,4R,5S,6E)-5-[(4-Methoxybenzyl)oxy]-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-6-heptene-1,3-diol	C₃₃H₅₈O₆Si	详情	详情
(VIII)	11575	2-[(4S,5S,6S)-2-(4-Methoxyphenyl)-6-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-5-methyl-1,3-dioxan-4-yl]-1-ethanol	C₃₃H₅₆O₆Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：

The chiral unsaturated aldehyde intermediate (XXV) has been obtained as follows. The reaction of the chiral lactone (XVII) first with N,O-dimethylhydroxylamine and then with PmbO-(C=NH)CCl3 gives the Weinreb amide (XVIII), which is reduced with Bu2AlH to yield the butyraldehyde (XIX). The condensation of (XIX) with phosphorane (XX) affords the unsaturated ester (XXI), which is reduced with Bu2AlH to provide the unsaturated alcohol (XXII). The reaction of (XXII) with TrCl and lutidine gives the trityl ether (XXIII), which is desilylated by means of TBAF to yield the primary alcohol (XXIV). Finally, this compound is oxidized with DMP to afford the desired unsaturated aldehyde intermediate (XXV).

参考文献中间体

合成目标

【1】 Nelson, S.G.; Cheung, W.S.; Kassick, A.J.; Hilfiker, M.A.; A de novo enantioselective total synthesis of (-)-laulimalide. J Am Chem Soc 2002, 124, 46, 13654.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	63307	1,1,1-trichloro-3-(4-methoxyphenyl)-2-propanimine		C₁₀H₁₀Cl₃NO	详情	详情
(XVII)	63880	4-{[tert-butyl(diphenyl)silyl]oxy}-2-oxetanone		C₁₉H₂₂O₃Si	详情	详情
(XVIII)	63881	(3S)-4-{[tert-butyl(diphenyl)silyl]oxy}-N-methoxy-3-[(4-methoxybenzyl)oxy]-N-methylbutanamide		C₃₀H₃₉NO₅Si	详情	详情
(XIX)	63882	(3S)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-[(4-methoxybenzyl)oxy]butanal		C₂₈H₃₄O₄Si	详情	详情
(XX)	14182	ethyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (Carbethoxymethylene)triphenylphosphorane	1099-45-2	C₂₂H₂₁O₂P	详情	详情
(XXI)	63884	ethyl (E,5S)-6-{[tert-butyl(diphenyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-2-hexenoate		C₃₂H₄₀O₅Si	详情	详情
(XXII)	63885	(E,5S)-6-{[tert-butyl(diphenyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-2-hexen-1-ol		C₃₀H₃₈O₄Si	详情	详情
(XXIII)	63883	tert-butyl(diphenyl)silyl (2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexenyl ether; tert-butyl{[(2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexenyl]oxy}diphenylsilane		C₄₉H₅₂O₄Si	详情	详情
(XXIV)	63886	(2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexen-1-ol		C₃₃H₃₄O₄	详情	详情
(XXV)	63887	(2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexenal		C₃₃H₃₂O₄	详情	详情

Extended Information