• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】34519

【品名】2-(2-benzyl-4-methoxyphenyl)acetyl chloride

【CA登记号】

【 分 子 式 】C16H15ClO2

【 分 子 量 】274.7466

【元素组成】C 69.95% H 5.5% Cl 12.9% O 11.65%

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:(VI)

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.

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:(VI)

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).

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 CAS号 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