benzyl acetate -Drug Synthesis Database

【结构式】

【分子编号】35457

【品名】benzyl acetate

【CA登记号】140-11-4

【分子式】C₉H₁₀O₂

【分子量】150.1772

【元素组成】C 71.98% H 6.71% O 21.31%

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：(VII)

The hydrolysis of the ketoester (I) with NaOH gives the corresponding ketoacid (II), which is condensed with 4-nitrobenzaldehyde (III) by means of pyridine to yield the hydroxyketone (IV). The reaction of (IV) with acetic anhydride and pyridine affords the acetoxy compound (V), which is dehydrated by means of hot pyridine to provide the enone (VI). The condensation of (VI) with benzyl acetate (VII) by means of LDA gives 3-hydroxy-3-isopropyl-5-(4-nitrophenyl)-4-pentenoic acid benzyl ester (VIII), which is fully hydrogenated with H2 over Pd(OH)2 to yield the amino acid (IX). Finally, (IX) is treated with acetic anhydride to afford the target 5-(4-acetamidophenyl)-3-hydroxy-3-isopropylpentanoic acid intermediate (X).

参考文献中间体

合成目标

【1】 Deering, C.F.; et al.; Application of the Schöpf method to optimization of the synthesis of 3-[2-(p-N-acetylaminophenyl)ethyl]-3-hydroxy-4-methylpentanoic acid: Simultaneous reduction of three functional groups to maximine yield and throughput. Org Process Res Dev 2000, 4, 6, 596.

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)	43331	methyl 4-methyl-3-oxopentanoate	42558-54-3	C₇H₁₂O₃	详情	详情
(II)	50030	4-methyl-3-oxopentanoic acid		C₆H₁₀O₃	详情	详情
(III)	18184	4-Nitrobenzaldehyde	555-16-8	C₇H₅NO₃	详情	详情
(IV)	50031	1-hydroxy-4-methyl-1-(4-nitrophenyl)-3-pentanone		C₁₂H₁₅NO₄	详情	详情
(V)	50032	4-methyl-1-(4-nitrophenyl)-3-oxopentyl acetate		C₁₄H₁₇NO₅	详情	详情
(VI)	50033	(E)-4-methyl-1-(4-nitrophenyl)-1-penten-3-one		C₁₂H₁₃NO₃	详情	详情
(VII)	35457	benzyl acetate	140-11-4	C₉H₁₀O₂	详情	详情
(VIII)	50034	benzyl (E)-3-hydroxy-3-isopropyl-5-(4-nitrophenyl)-4-pentenoate		C₂₁H₂₃NO₅	详情	详情
(IX)	50035	3-(4-aminophenethyl)-3-hydroxy-4-methylpentanoic acid		C₁₄H₂₁NO₃	详情	详情
(X)	50036	3-[4-(acetamido)phenethyl]-3-hydroxy-4-methylpentanoic acid		C₁₆H₂₃NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of 5-(4-hydroxyphenyl)-2-methyl-3-pentanone (I) with benzyl acetate (II) by means of LDA in THF gives 3-hydroxy-5-(4-hydroxyphenyl)-3-isopropylpentanoic acid benzyl ester (III), which is treated with H2 over Pd/C in methanol to yield the corresponding free acid (IV) as a racemic mixture. Optical resolution of (IV) with (S)-alpha-methylbenzylamine ((S)-MBA) affords the (S)-isomer (V), which is cyclized with the magnesium salt of the monoethyl malonate by means of CDI in THF giving 4-hydroxy-6(S)-[2-(4-hydroxyphenyl)ethyl]-6-isopropyl-5,6-dihydro-2H-pyran-2-one (VI). Finally, this compound is condensed with toluene-4-thiosulfonic acid S-(4-amino-2-tert-butyl-5-methylphenyl) ester (VII) by means of K2CO3 in DMF.

参考文献中间体

合成目标

【1】 Vara Prasad, J.V.N.; Domagala, J.M.; Boyer, F.E.; et al.; 5,6-Dihydropyran-2-ones possessing various sulfonyl functionalities: Potent nonpeptidic inhibitors of HIV protease. J Med Chem 2000, 43, 5, 843.

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)	35456	1-(4-hydroxyphenyl)-4-methyl-3-pentanone		C₁₂H₁₆O₂	详情	详情
(II)	35457	benzyl acetate	140-11-4	C₉H₁₀O₂	详情	详情
(III)	35458	benzyl 3-hydroxy-3-(4-hydroxyphenethyl)-4-methylpentanoate		C₂₁H₂₆O₄	详情	详情
(IV)	35459	3-hydroxy-3-(4-hydroxyphenethyl)-4-methylpentanoic acid		C₁₄H₂₀O₄	详情	详情
(V)	35460	(3S)-3-hydroxy-3-(4-hydroxyphenethyl)-4-methylpentanoic acid		C₁₄H₂₀O₄	详情	详情
(VI)	35461	(6S)-4-hydroxy-6-(4-hydroxyphenethyl)-6-isopropyl-5,6-dihydro-2H-pyran-2-one		C₁₆H₂₀O₄	详情	详情
(VII)	35462	S-[4-amino-2-(tert-butyl)-5-methylphenyl] 4-methylbenzenesulfonothioate		C₁₈H₂₃NO₂S₂	详情	详情

Extended Information