3-Methoxyphenol -Drug Synthesis Database

【结构式】

【分子编号】22389

【品名】3-Methoxyphenol

【CA登记号】150-19-6

【分子式】C₇H₈O₂

【分子量】124.13932

【元素组成】C 67.73% H 6.5% O 25.78%

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：(VI)

Friedel Crafts condensation of p-dimethoxybenzene (I) with dichloromaleic anhydride (II) in a molten mixture of AlCl3 and NaCl yielded dichloronaphthazarin (III). Subsequent methylation of (III) with CH3I in the presence of Ag2O in CHCl3 gave a mixture of dimethoxy naphthoquinones (IV) and (V), from which the desired isomer (IV) was isolated by recrystallization from CHCl3-CCl4. Finally, treatment of (IV) with 3-methoxyphenol (VI) and Na2CO3 in DMSO at room temperature furnished the target compound.

参考文献中间体

合成目标

【1】 Chang, H.-X.; Chou, T.C.; Savaraj, N.; Liu, L.F.; Yu, C.; Cheng, C.C.; Design of antineoplastic agents based on the "2-phenylnaphthalene-type" structural pattern. 4. Synthesis and biological activity of 2-chloro-3-(substituted phenoxy)-1,4-naphthoquinones and related 5,8-dihydroxy-1,4-naphthoquinones. J Med Chem 1999, 42, 3, 405.

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)	21946	1,4-dimethoxybenzene; 4-methoxyphenyl methyl ether	150-78-7	C₈H₁₀O₂	详情	详情
(II)	21947	3,4-dichloro-2,5-furandione	1122-17-4	C₄Cl₂O₃	详情	详情
(III)	21948	2,3-dichloro-5,8-dihydroxynaphthoquinone	14918-69-5	C₁₀H₄Cl₂O₄	详情	详情
(IV)	21951	2,3-dichloro-5,8-dimethoxynaphthoquinone		C₁₂H₈Cl₂O₄	详情	详情
(V)	21950	6,7-dichloro-5,8-dimethoxynaphthoquinone		C₁₂H₈Cl₂O₄	详情	详情
(VI)	22389	3-Methoxyphenol	150-19-6	C₇H₈O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Friedel-Crafts acylation of 3-methoxyphenol (I) with 4-hydroxyphenylacetic acid (II) in the presence of ZnCl2 and POCl3 furnished ketone (III), which was subsequently protected with triisopropylsilyl chloride and Et3N to yield the mono-silyl ether (IV). Coumarin (VI) was then synthesized by condensation of hydroxy ketone (IV) with phenylacetyl chloride (V) in the presence of K2CO3. Alkylation of the phenolic hydroxyl group of (VI) with N-(2-chloroethyl)piperidine (VII) gave the piperidinylethyl ether (VIII). Finally, selective methyl ether hydrolysis using HBr in refluxing HOAc led to the title compound.

参考文献中间体

合成目标

【1】 Bhagwat, S.S.; McKie, J.A.; Khammungkhune, S. (Signal Pharmaceuticals, Inc.); Cpds. and methods for modulation of estrogen receptors. WO 0149673 .

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)	22389	3-Methoxyphenol	150-19-6	C₇H₈O₂	详情	详情
(II)	18430	2-(4-Hydroxyphenyl)acetic acid; 4-Hydroxyphenylacetic acid	156-38-7	C₈H₈O₃	详情	详情
(III)	56078	1-(2-hydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl)-1-ethanone		C₁₅H₁₄O₄	详情	详情
(IV)	56079	1-(2-hydroxy-4-methoxyphenyl)-2-{4-[(triisopropyl-lambda~4~-sulfanyl)oxy]phenyl}-1-ethanone		C₂₄H₃₄O₄S	详情	详情
(V)	25890	2-phenylacetyl chloride；Phenylacetyl chloride;Phenacetyl chloride;Benzeneacetyl chloride	103-80-0	C₈H₇ClO	详情	详情
(VI)	56080	4-(4-hydroxybenzyl)-7-methoxy-3-phenyl-2H-chromen-2-one		C₂₃H₁₈O₄	详情	详情
(VII)	10117	1-(2-Chloroethyl)piperidine; N-(2-Chloroethyl)piperidine	1932-03-2	C₇H₁₄ClN	详情	详情
(VIII)	56081	7-methoxy-3-phenyl-4-{4-[2-(1-piperidinyl)ethoxy]benzyl}-2H-chromen-2-one		C₃₀H₃₁NO₄	详情	详情

Extended Information