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【结 构 式】

【分子编号】23171

【品名】bromo[4-(diethoxymethyl)phenyl]magnesium

【CA登记号】

【 分 子 式 】C11H15BrMgO2

【 分 子 量 】283.4479

【元素组成】C 46.61% H 5.33% Br 28.19% Mg 8.57% O 11.29%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(II)

The reaction of 3-chloromethylpyridine (I) with the Grignard reagent of 4-bromobenzaldehyde diethylacetal (II) in THF gives 4-(3-pyridylmethyl)benzaldehyde diethylacetal (III), which is hydrolyzed with aqueous 1N HCl to 4-(3-pyridylmethyl)benzaldehyde (IV). The Wittig condensation of (IV) with 1-(ethoxycarbonyl)ethylidenetriphenylphosphorane (V) in CHCl3 affords 3-[4-(3-pyridylmethyl)phenyl]-2-methylacryl ic acid ethyl ester (VI), which is finally hydrolyzed with aqueous NaOH.

1 Tanouchi, T.; et al.; Pyridine derivatives. DE 2951786; FR 2445319; FR 2510108; GB 2039903; US 4271170; US 4317828 .
2 Hillier, K.; Serradell, M.N.; Blancafort, P.; Castaner, J.; OKY-1581. Drugs Fut 1982, 7, 6, 399.
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) 15793 3-(Chloromethyl)pyridine 3099-31-8 C6H6ClN 详情 详情
(II) 23171 bromo[4-(diethoxymethyl)phenyl]magnesium C11H15BrMgO2 详情 详情
(III) 37069 3-[4-(diethoxymethyl)benzyl]pyridine; ethoxy[4-(3-pyridinylmethyl)phenyl]methyl ethyl ether C17H21NO2 详情 详情
(IV) 37070 4-(3-pyridinylmethyl)benzaldehyde C13H11NO 详情 详情
(V) 37071 ethyl 2-(triphenylphosphoranylidene)propanoate 5717-37-3 C23H23O2P 详情 详情
(VI) 37072 ethyl (E)-2-methyl-3-[4-(3-pyridinylmethyl)phenyl]-2-propenoate C18H19NO2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

Oxidation of disulfide (I) with sulfuryl chloride in AcOH at -20 C afforded (4-methoxyphenyl)sulfinyl chloride (II), which was condensed with (1R,2S)-2-phenylcyclohexanol to provide sulfinate (IV) as a single diastereomer. Subsequent condensation with the Grignard reagent (V) produced the chiral sulfoxide (VI). The diethyl acetal of (VI) was then hydrolyzed to the corresponding benzaldehyde (VII) using p-TsOH in THF-H2O. Finally, condensation of (VII) with N-cyclohexylpiperazine (VIII) using titanium tetraisopropoxide, followed by addition of diethylaluminum cyanide, furnished the target piperazinylacetonitrile.

1 Lowe, D.B.; Guzik, H.S.; Kozlowski, J.A.; et al.; Diphenyl sulfoxides as selective antagonists of the muscarinic M2 receptor. Bioorg Med Chem Lett 2000, 10, 20, 2255.
2 Lowe, D.; Chang, W.; Kozlowski, J.; Berger, J.G.; McQuade, R.; Barnett, A.; Scherlock, M.; Tom, W.; Dugar, S.; Chen, L.-Y.; Clader, J.W.; Chackalamannil, S. (Schering Corp.); Benzylpiperidines and piperazines as muscarinic an. EP 0811002; JP 1999501014; US 5883096; WO 9626196 .
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) 23167 1-methoxy-4-[(4-methoxyphenyl)disulfanyl]benzene; bis(4-methoxyphenyl) disulfide 5335-87-5 C14H14O2S2 详情 详情
(II) 23168 4-methoxybenzenesulfinyl chloride C7H7ClO2S 详情 详情
(III) 23169 (1S,2R)-2-phenylcyclohexanol C12H16O 详情 详情
(IV) 23170 (1S,2R)-2-phenylcyclohexyl 4-methoxybenzenesulfinate C19H22O3S 详情 详情
(V) 23171 bromo[4-(diethoxymethyl)phenyl]magnesium C11H15BrMgO2 详情 详情
(VI) 23172 [4-(diethoxymethyl)phenyl](4-methoxyphenyl)oxo-lambda(4)-sulfane; 4-(diethoxymethyl)phenyl 4-methoxyphenyl sulfoxide C18H22O4S 详情 详情
(VII) 23173 4-[(4-methoxyphenyl)sulfinyl]benzaldehyde C14H12O3S 详情 详情
(VIII) 23174 1-cyclohexylpiperazine 17766-28-8 C10H20N2 详情 详情
Extended Information