1-ethoxy-2,2,2-trifluoro-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】26582

【品名】1-ethoxy-2,2,2-trifluoro-1-ethanol

【CA登记号】433-27-2

【分子式】C₄H₇F₃O₂

【分子量】144.0935896

【元素组成】C 33.34% H 4.9% F 39.55% O 22.21%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VI)

The intermediate mixed anhydride (V) has been obtained as follows: the condensation of 2-nitroimidazole (I) with methyl 2-bromoacetate (II) by means of NaOMe in methanol gives 2-(2-nitro-1H-imidazol-1-yl)acetic acid methyl ester (III), which is hydrolyzed with NaOH to yield the corresponding acid (IV). Finally, this compound is condensed with isobutyl chloroformate by means of NMM in THF to afford the desired mixed anhydride intermediate (V). The condensation of 2,2,2-trifluoroacetaldehyde ethyl hemiacetal (VI) with nitromethane (VII) by means of K2CO3 gives 1,1,1-trifluoro-3-nitro-2-propanol (VIII), which is reduced with H2 over RaNi in ethanol to yield 3-amino-1,1,1-trifluoro-2-propanol (IX). Finally, this compound is condensed with the mixed anhydride intermediate (V) by means of NMM in THF to afford the target amide.

参考文献中间体

合成目标

【1】 Tracy, M.; Kelson, A.B.; Workman, P.; Lewis, A.D.; Aboagye, E.O. (Cancer Research UK; SRI International); Fluorinated 2-nitroimidazole analogs for detecting hypoxic tumor cells. EP 0775117; JP 1998506104; US 5721265; WO 9604249 .

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)	10145	2-Nitro-1H-imidazole; 2-Nitroimidazole	527-73-1	C₃H₃N₃O₂	详情	详情
(II)	12309	methyl 2-bromoacetate; methyl bromoacetate	96-32-2	C₃H₅BrO₂	详情	详情
(III)	10258	methyl 2-(2-nitro-1H-imidazol-1-yl)acetate; Methyl 2-nitro-1-imidazoleacetate	22813-31-6	C₆H₇N₃O₄	详情	详情
(IV)	56733	2-(2-nitro-1H-imidazol-1-yl)acetic acid		C₅H₅N₃O₄	详情	详情
(V)	56734			C₁₀H₁₃N₃O₆	详情	详情
(VI)	26582	1-ethoxy-2,2,2-trifluoro-1-ethanol	433-27-2	C₄H₇F₃O₂	详情	详情
(VII)	39563	nitromethane	75-52-5	CH₃NO₂	详情	详情
(VIII)	56735	1,1,1-trifluoro-3-nitro-2-propanol		C₃H₄F₃NO₃	详情	详情
(IX)	56736	3-amino-1,1,1-trifluoro-2-propanol	431-38-9	C₃H₆F₃NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Reaction of benzaldehyde (I) with trimethylsilyl cyanide and ZnI2 gave O-trimethylsilyl cyanohydrin (II). Subsequent condensation of (II) with 4-(methylthio)benzaldehyde (III) in the presence of lithium hexamethyldisilazide, followed by quenching of the intermediate (IV) with KHF2 and HCl, provided benzoin (V). This was oxidized either under Swern conditions, or with Bi2O3 in acetic to afford the corresponding benzil (VI). Condensation of (VI) with trifluoroacetaldehyde ethyl hemiacetal (VII) produced imidazole (VIII). Finally, oxidation of the sulfide group of (VIII) with hydrogen peroxide in AcOH provided the target sulfone.

参考文献中间体

合成目标

【1】 Barta, T.E.; Collins, P.W.; Weier, R.M.; Stealey, M.A.; Antiinflammatory 4,5-diarylimidazoles as selective cyclooxygenase inhibitors. Bioorg Med Chem Lett 1998, 8, 24, 3443.
【2】 Weier, R.M.; Collins, P.W.; Stealey, M.A.; Barta, T.E.; Huff, R.M. (Pharmacia Corp.); 4,5-Substd. imidazolyl cpds. for the treatment of inflammation. EP 0772601; US 5620999; WO 9603387 .

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)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(II)	26578	2-phenyl-3-(trimethylsilyl)propanenitrile		C₁₂H₁₇NSi	详情	详情
(III)	18815	4-(methylsulfanyl)benzaldehyde; 4-(methylmercapto)benzaldehyde	3446-89-7	C₈H₈OS	详情	详情
(IV)	26579	3-hydroxy-3-[4-(methylsulfanyl)phenyl]-2-phenyl-2-[(trimethylsilyl)methyl]propanenitrile		C₂₀H₂₅NOSSi	详情	详情
(V)	26580	2-hydroxy-2-[4-(methylsulfanyl)phenyl]-1-phenyl-1-ethanone		C₁₅H₁₄O₂S	详情	详情
(VI)	26581	1-[4-(methylsulfanyl)phenyl]-2-phenyl-1,2-ethanedione		C₁₅H₁₂O₂S	详情	详情
(VII)	26582	1-ethoxy-2,2,2-trifluoro-1-ethanol	433-27-2	C₄H₇F₃O₂	详情	详情
(VIII)	26583	methyl 4-[5-phenyl-2-(trifluoromethyl)-1H-imidazol-4-yl]phenyl sulfide		C₁₇H₁₃F₃N₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

An related procedure was based on the formation of the intermediate stilbene sulfone (XII) by Wittig reaction. Thus, condensation of phosphonium salt (IX) with aldehyde (X) in the presence of LiOEt gave stilbene (XI) as a mixture of geometric isomers. Then, oxidation of the sulfide group of (XI) with Oxone provided stilbene sulfone (XII). Alternatively, phosphonium salt (XIV), prepared from benzyl chloride (XIII) and triphenyl phosphine, was condensed with benzaldehyde to yield (XII). The oxidation of stilbene (XII) with KMnO4 produced benzil (XV). Finally, cyclization of (XV) with hemiacetal (VII) furnished the title imidazole.

参考文献中间体

合成目标

【1】 Barta, T.E.; Collins, P.W.; Weier, R.M.; Stealey, M.A.; Antiinflammatory 4,5-diarylimidazoles as selective cyclooxygenase inhibitors. Bioorg Med Chem Lett 1998, 8, 24, 3443.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(VII)	26582	1-ethoxy-2,2,2-trifluoro-1-ethanol	433-27-2	C₄H₇F₃O₂	详情	详情
(IX)	26584	benzyl(triphenyl)phosphonium iodide	15853-35-7	C₂₅H₂₂IP	详情	详情
(X)	18815	4-(methylsulfanyl)benzaldehyde; 4-(methylmercapto)benzaldehyde	3446-89-7	C₈H₈OS	详情	详情
(XI)	26585	methyl 4-[(Z)-2-phenylethenyl]phenyl sulfide		C₁₅H₁₄S	详情	详情
(XII)	26586	methyl 4-[(Z)-2-phenylethenyl]phenyl sulfone		C₁₅H₁₄O₂S	详情	详情
(XIII)	26587	4-(chloromethyl)phenyl methyl sulfone		C₈H₉ClO₂S	详情	详情
(XIV)	26588	[4-(methylsulfonyl)benzyl](triphenyl)phosphonium chloride		C₂₆H₂₄ClO₂PS	详情	详情
(XV)	26589	1-[4-(methylsulfonyl)phenyl]-2-phenyl-1,2-ethanedione		C₁₅H₁₂O₄S	详情	详情

Extended Information