2-(4-acetylphenoxy)-5-methylbenzoic acid -Drug Synthesis Database

【结构式】

【分子编号】34152

【品名】2-(4-acetylphenoxy)-5-methylbenzoic acid

【CA登记号】

【分子式】C₁₆H₁₄O₄

【分子量】270.28476

【元素组成】C 71.1% H 5.22% O 23.68%

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：(III)

The reaction of 2-iodo-5-methylbenzoic acid (I) with 4-hydroxyacetophenone (II) by means of K2CO3 in nitrobenzene at 150 C gives 2-(4-acetylphenoxy)-5-methylbenzoic acid (III), which by reduction with LiAlH4 in refluxing THF is converted into 2-[4-(1-hydroxyethyl)phenoxy]-5-methylbenzyl alcohol (IV). The reaction of (IV) with SOCl2 in refluxing CHCl3 affords 2-[4-(1-chloroethyl)phenoxy]-5-methylbenzyl chloride (V), which is treated with NaCN in refluxing dioxane ethanol-water yielding the dinitrile (VI). The hydrolysis of (VI) with KOH in refluxing ethanol-water gives 2-[4-[2-(carboxymethyl)-4-methylphenoxy]phenyl]propionic acid (VII), which is finally cyclized by treatment with polyphosphoric acid (PPA) at 120 C.

参考文献中间体

合成目标

【1】 Uno, H.; Nagai, Y.; Nakamura, H.; Dibenz[b,f]oxepin and dibenzo[b,f]thiepin derivatives, process for preparation thereof, method of using the same, and compositions thereof. EP 0003893; ES 477791; JP 1393170C; JP 54122284; US 4238620 .
【2】 Serradell, M.N.; Arrigoni-Martelli, E.; Castaner, J.; AD-1590. Drugs Fut 1984, 9, 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)	34151	2-iodo-5-methylbenzoic acid	52548-14-8	C₈H₇IO₂	详情	详情
(II)	18123	1-(4-hydroxyphenyl)-1-ethanone; 4'-Hydroxyacetophenone	99-93-4	C₈H₈O₂	详情	详情
(III)	34152	2-(4-acetylphenoxy)-5-methylbenzoic acid		C₁₆H₁₄O₄	详情	详情
(IV)	34153	1-[4-[2-(hydroxymethyl)-4-methylphenoxy]phenyl]-1-ethanol		C₁₆H₁₈O₃	详情	详情
(V)	34154	1-[4-(1-chloroethyl)phenoxy]-2-(chloromethyl)-4-methylbenzene; 4-(1-chloroethyl)phenyl 2-(chloromethyl)-4-methylphenyl ether		C₁₆H₁₆Cl₂O	详情	详情
(VI)	34155	2-[4-[4-methyl-2-(2-nitriloethyl)phenoxy]phenyl]propanenitrile		C₁₈H₁₆N₂O	详情	详情
(VII)	34156	2-[4-[2-(2-hydroxy-2-oxoethyl)-4-methylphenoxy]phenyl]propionic acid		C₁₈H₁₈O₅	详情	详情

Extended Information