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【结 构 式】

【分子编号】50508

【品名】methyl 3-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]propanoate

【CA登记号】

【 分 子 式 】C27H28Cl2O4S

【 分 子 量 】519.48832

【元素组成】C 62.43% H 5.43% Cl 13.65% O 12.32% S 6.17%

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:(VII)

Condensation of 4,4'-dichlorobenzhydrol (I) with 2-bromoethanol (II) in the presence of sulfuric acid gave the bromopropyl ether (III), which was further condensed with 2-mercaptoethanol (IV), yielding thioether (V). Subsequent coupling of alcohol (V) with methyl 3-(4-hydroxyphenyl)propionate (VI) under Mitsunobu conditions furnished adduct (VII). Basic hydrolysis of the methyl ester function generated acid (VIII). After conversion of (VIII) to the corresponding acid chloride, its condensation with trifluoroacetic anhydride gave rise to the trifluoromethyl ketone (IX). The sulfide group of (X) was finally oxidized to the title sulfone using meta-chloroperbenzoic acid.

1 Banville, J.; Burke, J.R.; Gai, Y.; Johnson, G.; Zusi, F.C. (Bristol-Myers Squibb Co.); Selective cPLA2 inhibitors. EP 1140791; WO 9915129 .
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) 50505 4,4'-Dichlorobenzhydrol; Bis(4-chlorophenyl)carbinol 90-97-1 C13H10Cl2O 详情 详情
(II) 10059 Ethylene bromohydrin; 2-Bromo-1-ethanol 540-51-2 C2H5BrO 详情 详情
(III) 50506 1-[(2-bromoethoxy)(4-chlorophenyl)methyl]-4-chlorobenzene; bis(4-chlorophenyl)methyl 2-bromoethyl ether C15H13BrCl2O 详情 详情
(IV) 36375 2-Sulfanyl-1-ethanol; 2-Mercaptoethanol 60-24-2 C2H6OS 详情 详情
(V) 50507 2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)-1-ethanol C17H18Cl2O2S 详情 详情
(VI) 30341 methyl 3-(4-hydroxyphenyl)propanoate; 4-Hydroxyphenylpropionic acid methyl ester; 3-(4-Hydroxyphenyl)propionic acid methyl ester 5597-50-2 C10H12O3 详情 详情
(VII) 50508 methyl 3-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]propanoate C27H28Cl2O4S 详情 详情
(VIII) 50509 3-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]propionic acid C26H26Cl2O4S 详情 详情
(IX) 50510 4-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]-1,1,1-trifluoro-2-butanone C27H25Cl2F3O3S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VII)

The hydrolysis of the known thioacetate (I) with NaOH in THF gives the thiol (II), which is condensed with 14C-labelled bromoacetic acid (III) by means of NaOH in water to yield the sulfanyl-acetic acid (IV). The reduction of (IV) with LiAlH4 in THF affords the sulfanylethanol derivative (V); which is condensed with 3-(4-hydroxyphenyl)propionic acid methyl ester (VI) by means of DEAD and PPh3 in toluene to provide the labelled aryl ether (VII).The hydrolysis of the ester group of (VII) by means of KOH in ethanol/water gives the propionic acid (VIII), which is converted into the trifluoromethyl ketone (IX) by reaction with oxalyl chloride, trifluoroacetic anhydride and pyridine in toluene/dichloromethane. Finally, the oxidation of the sulfanyl group of (IX) with MCPBA in dichloromethane affords the target labelled sulfone.

1 Dischino, D.D.; Banville, J.; Remillard, R.; Synthesis of carbon-14 labeled 4-[4-[2-[2-[bis(4-chlorophenyl)methoxy]ethylsulfonyl][1-14C]ethoxy]phenyl]-1,1,1-trifluoro-2-butanone. J Label Compd Radiopharm 2003, 46, 2, 167.
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) 64511 S-{2-[bis(4-chlorophenyl)methoxy]ethyl} ethanethioate C17H16Cl2O2S 详情 详情
(II) 64512 2-[bis(4-chlorophenyl)methoxy]ethylhydrosulfide; 2-[bis(4-chlorophenyl)methoxy]-1-ethanethiol C15H14Cl2OS 详情 详情
(III) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(III) 64514 2-bromoacetic acid C2H3BrO2 详情 详情
(IV) 64513 2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)acetic acid C17H16Cl2O3S 详情 详情
(IV) 64515 2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)acetic acid C17H16Cl2O3S 详情 详情
(V) 50507 2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)-1-ethanol C17H18Cl2O2S 详情 详情
(V) 64516 2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)-1-ethanol C17H18Cl2O2S 详情 详情
(VI) 30341 methyl 3-(4-hydroxyphenyl)propanoate; 4-Hydroxyphenylpropionic acid methyl ester; 3-(4-Hydroxyphenyl)propionic acid methyl ester 5597-50-2 C10H12O3 详情 详情
(VII) 50508 methyl 3-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]propanoate C27H28Cl2O4S 详情 详情
(VII) 64517 methyl 3-{4-[2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)ethoxy]phenyl}propanoate C27H28Cl2O4S 详情 详情
(VIII) 50509 3-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]propionic acid C26H26Cl2O4S 详情 详情
(VIII) 64518 3-{4-[2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)ethoxy]phenyl}propanoic acid C26H26Cl2O4S 详情 详情
(IX) 50510 4-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]-1,1,1-trifluoro-2-butanone C27H25Cl2F3O3S 详情 详情
(IX) 64519 4-{4-[2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)ethoxy]phenyl}-1,1,1-trifluoro-2-butanone C27H25Cl2F3O3S 详情 详情
Extended Information