(2E,4E)-5-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-pentadienal -Drug Synthesis Database

【结构式】

【分子编号】41334

【品名】(2E,4E)-5-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-pentadienal

【CA登记号】

【分子式】C₁₄H₁₂F₄O₂

【分子量】288.2416928

【元素组成】C 58.34% H 4.2% F 26.36% O 11.1%

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：(VI)

4-Hydroxybenzaldehyde (I) was alkylated with 2,2,3,3-tetrafluoropropyl tosylate (A) to give ether (II). Subsequent Horner-Emmons condensation of (II) with triethyl phosphonocrotonate (III) provided dienoate (IV), that was further reduced to alcohol (V) by means of DIBAL. Oxidation of (V) with activated MnO2 then gave aldehyde (VI).

参考文献中间体

合成目标

【1】 Tajima, Y.; Oida, S.; Konosu, T.; et al.; Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives. Chem Pharm Bull 2000, 48, 5, 694.
【2】 Oida, S.; Tanaka, T.; Tajima, Y.; Konosu, T.; Somada, A.; Miyaoka, T.; Yasuda, H. (Sankyo Co., Ltd.); Triazole antifungal agent. EP 0841327; JP 1996333350; US 5977152; WO 9631491 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	41331	2,2,3,3-tetrafluoropropyl 4-methylbenzenesulfonate		C₁₀H₁₀F₄O₃S	详情	详情
(I)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(II)	15481	4-(2,2,3,3-tetrafluoropropoxy)benzaldehyde		C₁₀H₈F₄O₂	详情	详情
(III)	27705	methyl 4-amino-2-(1-naphthyl)benzoate		C₁₈H₁₅NO₂	详情	详情
(IV)	41332	ethyl (2E,4E)-5-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-pentadienoate		C₁₆H₁₆F₄O₃	详情	详情
(V)	41333	(2E,4E)-5-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-pentadien-1-ol		C₁₄H₁₄F₄O₂	详情	详情
(VI)	41334	(2E,4E)-5-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-pentadienal		C₁₄H₁₂F₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Displacement of tosylate (VII) with sodium thioacetate afforded thioester (VIII) (1). Hydrolysis of the thioester (VIII) in the presence of NaOMe, followed by condensation of the intermediate thiol with the chiral epoxide (IX) furnished the mercapto alcohol (X). Hydrolysis of the cyclic acetal of (X) in methanolic HCl gave triol (XI). This was finally condensed with aldehyde (VI) in the presence of p-TsOH and molecular sieves to yield the title compound.

参考文献中间体

合成目标

【1】 Oida, S.; et al.; Synthesis and antifungal activity of R-102557, a novel dioxane-triazole compound. 19th Symp Med Chem (Nov 17 1999, Tokyo) 1999, Abst 2P-15.
【2】 Tajima, Y.; Oida, S.; Konosu, T.; et al.; Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives. Chem Pharm Bull 2000, 48, 5, 694.
【3】 Oida, S.; Tanaka, T.; Tajima, Y.; Konosu, T.; Somada, A.; Miyaoka, T.; Yasuda, H. (Sankyo Co., Ltd.); Triazole antifungal agent. EP 0841327; JP 1996333350; US 5977152; WO 9631491 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	41334	(2E,4E)-5-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-pentadienal	C₁₄H₁₂F₄O₂	详情	详情
(VII)	41335	2-phenyl-1,3-dioxan-5-yl 4-methylbenzenesulfonate	C₁₇H₁₈O₅S	详情	详情
(VIII)	41336	S-(2-phenyl-1,3-dioxan-5-yl) ethanethioate	C₁₂H₁₄O₃S	详情	详情
(IX)	31738	1-[[(2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole	C₁₂H₁₁F₂N₃O	详情	详情
(X)	41337	(2R,3R)-2-(2,4-difluorophenyl)-3-[(2-phenyl-1,3-dioxan-5-yl)sulfanyl]-1-(1H-1,2,4-triazol-1-yl)-2-butanol	C₂₂H₂₃F₂N₃O₃S	详情	详情
(XI)	41338	2-[[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]sulfanyl]-1,3-propanediol	C₁₅H₁₉F₂N₃O₃S	详情	详情

Extended Information