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【结 构 式】

【分子编号】54440

【品名】tert-butyl 2-(3-bromophenoxy)-2-methylpropanoate

【CA登记号】

【 分 子 式 】C14H19BrO3

【 分 子 量 】315.20706

【元素组成】C 53.35% H 6.08% Br 25.35% O 15.23%

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:(IV)

The reaction of 3-bromophenol (I) with 2,2,2-trichloro-1,1-dimethylethanol (II) by means of NaOH in acetone gives 2-(3-bromophenoxy)-2-methylpropionic acid (III), which is esterified with isobutylene and H2SO4, yielding the corresponding tert-butyl ester (IV). The condensation of (IV) with N-allylphthalimide (V) by means of Pd(OAc)2, tri(o-tolyl)phosphine and DIEA in acetonitrile, followed by hydrogenation with H2 over Pd/C, affords the adduct (VI). The reaction of (VI) with hydrazine in refluxing ethanol cleaves the phthalimido group to provide the amino derivative (VII), which is treated with 3,5-dinitrophenylsulfonyl chloride (VIII) and TEA in dichloromethane to give the sulfonamide (IX). The cleavage of the tert-butyl ester group of (IX) with TFA in dichloromethane yields the carboxylic acid (X), which is esterified with SASRIN resin (XI) by means of 1,3-dimethyl-2-fluoro p-toluenesulfonate (DMFPT) in dichloromethane to afford the resin-anchored polyester (XII). The N-alkylation of (XII) with 2,4-bis(trifluoromethyl)benzyl alcohol (XIII) by means of PPh3 and DIAD in THF provides the disubstituted sulfonamide (XIV). The cleavage of the sulfonamido group of (XIV) by means of mercaptoacetic acid and TEA in dichloromethane gives the resin-bound secondary amine (XV), which is acylated with 2-[4-(trifluoromethyl)phenyl]acetic acid (XVI) by means of HATU and DIEA to yield the acetamide precursor (XVII). Finally, the title product is cleaved from the resin (XVII) by treatment with TFA in dichloromethane.

1 Liu, K.G.; Lambert, M.H.; Leesnitzer, L.M.; et al.; Identification of a series of PPARgamma/delta dual agonists via solid-phase parallel synthesis. Bioorg Med Chem Lett 2001, 11, 22, 2959.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(X),(XII) 54445 2-[3-(3-{[(3,5-dinitrophenyl)sulfonyl]amino}propyl)phenoxy]-2-methylpropanoic acid C19H21N3O9S 详情 详情
(I) 20704 3-bromophenol 591-20-8 C6H5BrO 详情 详情
(II) 25975 1,1,1-trichloro-2-methyl-2-propanol 57-15-8 C4H7Cl3O 详情 详情
(III) 54439 2-(3-bromophenoxy)-2-methylpropanoic acid C10H11BrO3 详情 详情
(IV) 54440 tert-butyl 2-(3-bromophenoxy)-2-methylpropanoate C14H19BrO3 详情 详情
(V) 46464 2-allyl-1H-isoindole-1,3(2H)-dione C11H9NO2 详情 详情
(VI) 54441 tert-butyl 2-{3-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]phenoxy}-2-methylpropanoate C25H29NO5 详情 详情
(VII) 54442 tert-butyl 2-[3-(3-aminopropyl)phenoxy]-2-methylpropanoate C17H27NO3 详情 详情
(VIII) 54443 3,5-dinitrobenzenesulfonamide C6H5N3O6S 详情 详情
(IX) 54444 tert-butyl 2-[3-(3-{[(3,5-dinitrophenyl)sulfonyl]amino}propyl)phenoxy]-2-methylpropanoate C23H29N3O9S 详情 详情
(XIII) 54446 [2,4-bis(trifluoromethyl)phenyl]methanol C9H6F6O 详情 详情
(XIV) 54447 2-[3-(3-{[2,4-bis(trifluoromethyl)benzyl][(3,5-dinitrophenyl)sulfonyl]amino}propyl)phenoxy]-2-methylpropanoic acid C28H25F6N3O9S 详情 详情
(XV) 54448 2-[3-(3-{[2,4-bis(trifluoromethyl)benzyl]amino}propyl)phenoxy]-2-methylpropanoic acid C22H23F6NO3 详情 详情
(XVI) 54449 2-[4-(trifluoromethyl)phenyl]acetic acid 32857-62-8 C9H7F3O2 详情 详情
(XVII) 54450 2-{3-[3-([2,4-bis(trifluoromethyl)benzyl]{2-[4-(trifluoromethyl)phenyl]acetyl}amino)propyl]phenoxy}-2-methylpropanoic acid C31H28F9NO4 详情 详情
Extended Information