4-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]-1,1,1-trifluoro-2-butanone -Drug Synthesis Database

【结构式】

【分子编号】50510

【品名】4-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]-1,1,1-trifluoro-2-butanone

【CA登记号】

【分子式】C₂₇H₂₅Cl₂F₃O₃S

【分子量】557.4603096

【元素组成】C 58.17% H 4.52% Cl 12.72% F 10.22% O 8.61% S 5.75%

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：(IX)

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.

参考文献中间体

合成目标

【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：(IX)

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.

参考文献中间体

合成目标

【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