2-(2-benzyl-4-methoxyphenyl)acetic acid -Drug Synthesis Database

【结构式】

【分子编号】34518

【品名】2-(2-benzyl-4-methoxyphenyl)acetic acid

【CA登记号】

【分子式】C₁₆H₁₆O₃

【分子量】256.30124

【元素组成】C 74.98% H 6.29% O 18.73%

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：(V)

Addition of phenylmagnesium bromide to 6-methoxy-1-indanone (I) gave carbinol (II), which was dehydrated to phenylindene (III) upon treatment with p-toluenesulfonic acid in refluxing toluene. Oxidative cleavage of (III) with Jones reagent in the presence of OsO4 provided 2-benzoyl-4-methoxyphenylacetic acid (IV), which was further reduced to the 2-benzyl analogue (V) by hydrogenation over Pd/C. After conversion of (V) to the corresponding acid chloride (VI) using oxalyl chloride and a trace of DMF, Friedel-Crafts cyclization with AlCl3 furnished the dibenzocycloheptenone (VII). Addition of the lithium enolate of ethyl acetate to the carbonyl group of (VII) in the presence of tetramethylethylenediamine at -78 C generated the hydroxyester (VIII). Then, hydrogenolysis of the benzylic alcohol of (VIII) in the presence of Pd/C gave (IX). Subsequent cleavage of the methyl ether of (IX) by means of ethane thiol and AlCl3 provided the corresponding racemic phenol. Isolation of the required (S)-enantiomer (X) was carried out by chiral HPLC.

参考文献中间体

合成目标

【1】 Drake, F.H. (SmithKline Beecham plc); Method for stimulating bone formation. EP 0946180; WO 9815278 .
【2】 Miller, W.H.; Samanen, J.M.; Heerding, D.; Bondinell, W.E. (SmithKline Beecham Corp.); Vitronectin receptor antagonists. EP 1025090; WO 9915508 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	17491	ethyl acetate	141-78-6	C₄H₈O₂	详情	详情
	17616	bromo(phenyl)magnesium; Phenyl Magnesium Bromide	100-58-3	C₆H₅BrMg	详情	详情
(I)	34514	6-methoxy-1-indanone	13623-25-1	C₁₀H₁₀O₂	详情	详情
(II)	34515	6-methoxy-1-phenyl-1-indanol		C₁₆H₁₆O₂	详情	详情
(III)	34516	5-methoxy-3-phenyl-1H-indene; methyl 3-phenyl-1H-inden-5-yl ether		C₁₆H₁₄O	详情	详情
(IV)	34517	2-(2-benzoyl-4-methoxyphenyl)acetic acid		C₁₆H₁₄O₄	详情	详情
(V)	34518	2-(2-benzyl-4-methoxyphenyl)acetic acid		C₁₆H₁₆O₃	详情	详情
(VI)	34519	2-(2-benzyl-4-methoxyphenyl)acetyl chloride		C₁₆H₁₅ClO₂	详情	详情
(VII)	34520	3-methoxy-5,11-dihydro-10H-dibenzo[a,d]cyclohepten-10-one		C₁₆H₁₄O₂	详情	详情
(VIII)	34521	ethyl 2-(10-hydroxy-3-methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-yl)acetate		C₂₀H₂₂O₄	详情	详情
(IX)	34522	ethyl 2-(3-methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-yl)acetate		C₂₀H₂₂O₃	详情	详情
(X)	34523	ethyl 2-[(10S)-3-hydroxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-yl]acetate		C₁₉H₂₀O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

In a further procedure, 2-benzyl-4-methoxyphenol (XXII) was converted to triflate (XXIII), and then allylated to give (XXIV) using allyl tributyl tin. Cleavage of the allylic olefin with ruthenium tetroxide produced carboxylic acid (V). Formation of the acid chloride (VI), followed by Friedel-Crafts cyclization as above afforded tricyclic ketone (VII).

参考文献中间体

合成目标

【1】 Cousins, R.D.; Bondinell, W.E.; Miller, W.H.; et al.; Orally bioavailable nonpeptide vitronectin receptor antagonists with efficacy in an osteoporosis model. Bioorg Med Chem Lett 1999, 9, 13, 1807.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(V)	34518	2-(2-benzyl-4-methoxyphenyl)acetic acid	C₁₆H₁₆O₃	详情	详情
(VI)	34519	2-(2-benzyl-4-methoxyphenyl)acetyl chloride	C₁₆H₁₅ClO₂	详情	详情
(VII)	34520	3-methoxy-5,11-dihydro-10H-dibenzo[a,d]cyclohepten-10-one	C₁₆H₁₄O₂	详情	详情
(XXII)	34534	2-benzyl-4-methoxyphenol	C₁₄H₁₄O₂	详情	详情
(XXIII)	34535	2-benzyl-4-methoxyphenyl trifluoromethanesulfonate	C₁₅H₁₃F₃O₄S	详情	详情
(XXIV)	34536	4-allyl-3-benzylphenyl methyl ether; 1-allyl-2-benzyl-4-methoxybenzene	C₁₇H₁₈O	详情	详情

Extended Information