4-hydroxy-4-(4-hydroxybenzyl)-3-(4-methoxyphenyl)-3,4-dihydro-2H-chromen-7-yl pivalate -Drug Synthesis Database

【结构式】

【分子编号】65122

【品名】4-hydroxy-4-(4-hydroxybenzyl)-3-(4-methoxyphenyl)-3,4-dihydro-2H-chromen-7-yl pivalate

【CA登记号】

【分子式】C₂₈H₃₀O₆

【分子量】462.5426

【元素组成】C 72.71% H 6.54% O 20.75%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VIII)

The title compound is synthesized starting from the natural isoflavone formononetin (I). Esterification of (I) with pivaloyl chloride (II) affords pivalate (III). Catalytic hydrogenation of (III) in the presence of Pd/BaSO4 leads to the chromane derivative (IV). The Grignard reagent (VI), prepared from 4-(benzyloxy)benzyl chloride (V), is then condensed with ketone (IV) to furnish the tertiary alcohol (VII). The O-benzyl protecting group of (VII) is then removed by catalytic hydrogenolysis to afford phenol (VIII). Alkylation of (VIII) with N-(2-chloroethyl)piperidine (IX) and K2CO3, with simultaneous pivalate ester hydrolysis, leads to the piperidylethyl ether (X). The tertiary alcohol of (X) is finally dehydrated by means of HCl in acetonitrile to provide the target compound (1,2).

参考文献中间体

合成目标

【1】 Ghirardi, S.; Armani, E.; Amari, G.; Delcanale, M.; Civelli, M.; Caruso, P.; Galbiati, E.; Synthesis and pharmacological activity of CHF 4227, one of the most potent in vitro and in vivo SERMs till new discovered. Drugs Fut 2002, 27, Suppl. A.
【2】 Delcanale, M.; Civelli, M.; Armani, E.; Amari, G.; Galbiati, E. (Chiesi Farmaceutici SpA); 2H-1-Benzopyran derivs., processes for their preparation and pharmaceutical compsns. thereof. EP 1229036; EP 1281710; EP 1355906; WO 0259113 .

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)	65118	7-hydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one		C₁₆H₁₂O₄	详情	详情
(II)	13597	2,2-Dimethylpropanoyl chloride; Pivaloyl chloride	3282-30-2	C₅H₉ClO	详情	详情
(III)	65119	3-(4-methoxyphenyl)-4-oxo-4H-chromen-7-yl pivalate		C₂₁H₂₀O₅	详情	详情
(IV)	65120	3-(4-methoxyphenyl)-4-oxo-3,4-dihydro-2H-chromen-7-yl pivalate		C₂₁H₂₂O₅	详情	详情
(V)	65125	1-(benzyloxy)-4-(chloromethyl)benzene; benzyl 4-(chloromethyl)phenyl ether		C₁₄H₁₃ClO	详情	详情
(VI)	65124	[4-(benzyloxy)benzyl](chloro)magnesium		C₁₄H₁₃ClMgO	详情	详情
(VII)	65121	4-[4-(benzyloxy)benzyl]-4-hydroxy-3-(4-methoxyphenyl)-3,4-dihydro-2H-chromen-7-yl pivalate		C₃₅H₃₆O₆	详情	详情
(VIII)	65122	4-hydroxy-4-(4-hydroxybenzyl)-3-(4-methoxyphenyl)-3,4-dihydro-2H-chromen-7-yl pivalate		C₂₈H₃₀O₆	详情	详情
(IX)	10117	1-(2-Chloroethyl)piperidine; N-(2-Chloroethyl)piperidine	1932-03-2	C₇H₁₄ClN	详情	详情
(X)	65123	3-(4-methoxyphenyl)-4-{4-[2-(1-piperidinyl)ethoxy]benzyl}-4,7-chromanediol		C₃₀H₃₅NO₅	详情	详情

Extended Information