2-(acetamido)-2-[(acetoxy)methyl]-4-(4-octylphenyl)butyl acetate -Drug Synthesis Database

【结构式】

【分子编号】16712

【品名】2-(acetamido)-2-[(acetoxy)methyl]-4-(4-octylphenyl)butyl acetate

【CA登记号】

【分子式】C₂₅H₃₉NO₅

【分子量】433.5884

【元素组成】C 69.25% H 9.07% N 3.23% O 18.45%

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)

The Friedel-Crafts condensation of phenethyl acetate (I) with octanoyl chloride (II) by means of AlCl3 in dichloroethane gives 2-(4-octanoylphenyl)ethyl acetate (III), which is reduced with triethylsilane in TFA to afford 2-(4-octylphenyl)ethyl acetate (IV). The deprotection of (IV) with sodium ethoxide in ethanol gives 2-(4-octylphenyl)ethanol (V), which is treated with methanesulfonyl chloride followed by sodium iodide in refluxing 2-butanone yielding 2-(4-octylphenyl)ethyl iodide (VI). The condensation of (VI) with diethylacetamidomalonate (VII) by means of sodium ethoxide in ethanol/THF gives diethyl 2-acetamido-2-[2-(4-octylphenyl)ethyl]malonate (VIII), which is reduced with LiAlH4 in THF and treated with acetic anhydride in pyridine to afford 2-acetamido-2-(acetoxymethyl)-4-(4-octylphenyl)butyl acetate (IX). The hydrolysis of (IX) with lithium hydroxide in refluxing methanol/water gives 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol (X), which is finally treated with HCl in diethyl ether.

参考文献中间体

合成目标

【1】 Chiba, K.; Adachi, K.; FTY720. Drugs Fut 1997, 22, 1, 18.
【2】 Fujita, T.; Sasaki, S.; Yoneta, M.; Mishina, T.; Adachi, K.; Chiba, K. (Taito Co., Ltd.; Welfide Corporation); 2-Amino-1,3-propanediol compound and immunosuppressant. EP 0627406; JP 1994509845; US 5719176; WO 9408943 .
【3】 Kiuchi, M.; Adachi, K.; Kohara, T.; et al.; Synthesis and immunosuppressive activity of 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols. J Med Chem 2000, 43, 15, 2946.

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)	16704	phenethyl acetate; Phenylethyl-(2) Acetate	103-45-7	C₁₀H₁₂O₂	详情	详情
(II)	11123	Octanoyl chloride; n-Caprylyl chloride;Capryloyl chloride	111-64-8	C₈H₁₅ClO	详情	详情
(III)	16706	4-octanoylphenethyl acetate		C₁₈H₂₆O₃	详情	详情
(IV)	16707	4-octylphenethyl acetate		C₁₈H₂₈O₂	详情	详情
(V)	16708	2-(4-octylphenyl)-1-ethanol		C₁₆H₂₆O	详情	详情
(VI)	16709	1-[4-(2-iodoethyl)phenyl]octane		C₁₆H₂₅I	详情	详情
(VII)	16710	Diethyl 2-(acetamido)malonate; Diethyl acetamidomalonate	1068-90-2	C₉H₁₅NO₅	详情	详情
(VIII)	16711	diethyl 2-(acetamido)-2-(4-octylphenethyl)malonate		C₂₅H₃₉NO₅	详情	详情
(IX)	16712	2-(acetamido)-2-[(acetoxy)methyl]-4-(4-octylphenyl)butyl acetate		C₂₅H₃₉NO₅	详情	详情
(X)	16713	2-amino-2-(4-octylphenethyl)-1,3-propanediol	162359-55-9	C₁₉H₃₃NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

A new synthesis of FTY-720 has been described: The Friedel Crafts condensation of octylbenzene (I) with bromoacetyl chloride (II) by means of AlCl3 in dichloromethane gives the phenacyl bromide (III), which is condensed with 2-acetamidomalonic acid diethyl ester (IV) by means of EtONa in ethanol/THF to yielding the ketone-malonic ester adduct (V). Reduction of (V) with Et3SiH by means of TiCl4 in dichloromethane affords compound (VI), which is then reduced with LiAlH4 in THF followed by acetylation with acetic anhydride and pyridine to provide the acetate (VII). Finally, compound (VII) is hydrolyzed with LiOH in refluxing methanol/water and treated with HCl in ethyl ether.

参考文献中间体

合成目标

【1】 Renault, P.; Durand, P.; Peralba, P.; Sierra, F.; A new efficient synthesis of the immunosuppressive agent FTY-720. Synthesis 2000, 4, 505.

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)	43807	1-octylbenzene	2189-60-8	C₁₄H₂₂	详情	详情
(II)	27903	2-Bromoacetyl chloride	22118-09-8	C₂H₂BrClO	详情	详情
(III)	43808	2-bromo-1-(4-octylphenyl)-1-ethanone		C₁₆H₂₃BrO	详情	详情
(IV)	16710	Diethyl 2-(acetamido)malonate; Diethyl acetamidomalonate	1068-90-2	C₉H₁₅NO₅	详情	详情
(V)	43809	diethyl 2-(acetamido)-2-[2-(4-octylphenyl)-2-oxoethyl]malonate		C₂₅H₃₇NO₆	详情	详情
(VI)	16711	diethyl 2-(acetamido)-2-(4-octylphenethyl)malonate		C₂₅H₃₉NO₅	详情	详情
(VII)	16712	2-(acetamido)-2-[(acetoxy)methyl]-4-(4-octylphenyl)butyl acetate		C₂₅H₃₉NO₅	详情	详情

Extended Information