1-[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】38049

【品名】1-[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1-ethanol

【CA登记号】

【分子式】C₂₀H₃₄O₄Si

【分子量】366.57306

【元素组成】C 65.53% H 9.35% O 17.46% Si 7.66%

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 reaction of the acetonide of (R)-3,4-dihydroxybutanal (I) with the silylated 4-bromobenzyl alcohol (II) by means of n-BuLi in THF gives the corresponding carbinol (III), which is oxidized to the ethanone (IV) by means of tetrapropylammonium perruthenate (TPAP) and NMO in dichloromethane. The enantioselective reduction of the ketone (IV) by means of LiAlH4 and an excess of LiI in ethyl ether gives the (R,S)-enantiomer (V), which is mesylated with MsCl/TEA in dichloromethane and treated with NaN3 in hot DMF to yield the azide (VI). The reduction of (VI) with triphenylphosphine in THF/water affords the amine (VII), which is treated with allyl chloroformate and TEA in THF providing the carbamate (VIII). The desilylation of (VIII) with TBAF in THF gives the benzyl alcohol (IX), which is mesylated with MsCl and TEA in dichloromethane yielding the mesyl ester (X). The reaction of (X) with NaN3 in DMF affords the azide (XI), which is reduced as before to the benzylamine (XII). The reaction of (XII) with allyl chloroformate provides the bis carbamate (XIII).

参考文献中间体

合成目标

【1】 Imamura, H.; et al.; Discovery of novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenems. Bioorg Med Chem 2000, 8, 8, 1969.
【2】 Ohtake, N.; Imamura, H.; Shimizu, A.; et al.; Structure-activity relationships of trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenems. Part 1: J-111,347 and related compounds. Bioorg Med Chem Lett 2000, 10, 2, 109.
【3】 Imamura, H.; et al.; Synthesis of J-111,347, a novel 1beta-methylcarbapenem with broad-spectrum antibacterial activity. Chem Pharm Bull 2000, 48, 2, 310.
【4】 Ushijima, R.; Sugimoto, Y.; Shimizu, A.; Kiyonaga, H.; Nagano, R.; Nakagawa, S.; Sakuraba, S.; Sato, H.; Hashizume, T.; Nakano, M.; Imamura, H.; Fukatsu, H. (Banyu Pharmaceutical Co., Ltd.); Carbapenem derivs.. EP 1048669; JP 2000143512; WO 9931106 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	38047	2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]acetaldehyde	C₇H₁₂O₃	详情	详情
(II)	38048	[(4-bromobenzyl)oxy](tert-butyl)dimethylsilane; 4-bromobenzyl tert-butyl(dimethyl)silyl ether	C₁₃H₂₁BrOSi	详情	详情
(III)	38049	1-[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1-ethanol	C₂₀H₃₄O₄Si	详情	详情
(IV)	38050	1-[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1-ethanone	C₂₀H₃₂O₄Si	详情	详情
(V)	38051	(1S)-1-[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1-ethanol	C₂₀H₃₄O₄Si	详情	详情
(VI)	38052	[(4-[(1R)-1-azido-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]benzyl)oxy](tert-butyl)dimethylsilane; 4-[(1R)-1-azido-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]benzyl tert-butyl(dimethyl)silyl ether	C₂₀H₃₃N₃O₃Si	详情	详情
(VII)	38053	(1R)-1-[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1-ethanamine; (1R)-1-[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethylamine	C₂₀H₃₅NO₃Si	详情	详情
(VIII)	38054	allyl (1R)-1-[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethylcarbamate	C₂₄H₃₉NO₅Si	详情	详情
(IX)	38055	allyl (1R)-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1-[4-(hydroxymethyl)phenyl]ethylcarbamate	C₁₈H₂₅NO₅	详情	详情
(X)	38056	allyl (1R)-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1-[4-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)phenyl]ethylcarbamate	C₂₁H₃₁NO₅S	详情	详情
(XI)	38057	allyl (1R)-1-[4-(azidomethyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethylcarbamate	C₁₈H₂₄N₄O₄	详情	详情
(XII)	38058	allyl (1R)-1-[4-(aminomethyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethylcarbamate	C₁₈H₂₆N₂O₄	详情	详情
(XIII)	38059	allyl 4-[(1R)-1-[[(allyloxy)carbonyl]amino]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]benzylcarbamate	C₂₂H₃₀N₂O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The cyclization of 2-hydroxybenzaldehyde (I) with 2-(cyanacetamido)benzoic acid methyl ester (II) catalyzed by piperidine in ethanol gives the 2-imino-1-benzopyran (III), which is then hydrolyzed to the target benzopyranone with HCl in refluxing ethanol/water.

参考文献中间体

合成目标

【1】 Vasylyev, M.V.; Bilokin, Y.V.; Bylov, I.E.; Synthesis and antiinflammatory activity of N-substituted 2-oxo-2H-1-benzopyran-3-carboxamides and their 2-iminoanalagues. Eur J Med Chem 1999, 34, 11, 997.

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)	21351	2-Hydroxybenzaldehyde;Salicylic aldehyde；2-Formylphenol;salicylaldehyde	90-02-8	C₇H₆O₂	详情	详情
(II)	38049	1-[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl]-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1-ethanol		C₂₀H₃₄O₄Si	详情	详情
(III)	38410	methyl 2-[[(2-imino-2H-chromen-3-yl)carbonyl]amino]benzoate		C₁₈H₁₄N₂O₄	详情	详情

Extended Information