ethyl 4-formylbenzoate -Drug Synthesis Database

【结构式】

【分子编号】24495

【品名】ethyl 4-formylbenzoate

【CA登记号】

【分子式】C₁₀H₁₀O₃

【分子量】178.1876

【元素组成】C 67.41% H 5.66% O 26.94%

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)

The Friedel Kraft's acylation of 1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalene (I) with acetyl chloride by means of AlCl3 in nitrobenzene gives 2-acetyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (II), which is reduced with LiAlH4 in ether yielding 5,6,7,8-tetrahydro-alpha,5,5,8,8-pentamethylnaphthalene-2-methanol (III), The reaction of (III) with PBr3 in ether - hexane affords 2-(1-bromoethyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (IV), which by reaction with triphenylphosphine in hot xylene is converted into [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]triphenylphosphonium bromide (V). Finally, this compound is submitted to a Wittig condensation with ethyl 4-formylbenzoate (VI) in hot butylene oxide.

参考文献中间体

合成目标

【1】 Mayer, H.; Loeliger, P.; Bollag, W.; Arotinoids, a new class of highly active retinoids. Eur J Med Chem - Chim Ther 1980, 15, 1, 9-15.
【2】 Loeliger, P. (Hoffmann-La Roche, Inc.); Stilbene derivs.. US 4326055 .
【3】 Blancafort, P.; Hopkins, S.J.; Serradell, M.N.; Castaner, J.; RO-13-6298. Drugs Fut 1983, 8, 5, 432.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	36035	1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene	C₁₄H₂₀	详情	详情
(II)	36036	1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-ethanone	C₁₆H₂₂O	详情	详情
(III)	36037	1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-ethanol	C₁₆H₂₄O	详情	详情
(IV)	36038	6-(1-bromoethyl)-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene	C₁₆H₂₃Br	详情	详情
(V)	36039	triphenyl[1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)ethyl]phosphonium bromide	C₃₄H₃₈BrP	详情	详情
(VI)	24495	ethyl 4-formylbenzoate	C₁₀H₁₀O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The addition of methyl magnesium iodide to 2-acetylthiophene (I) and subsequent reduction of the propenyl derivative (II) with H2 over Pd/C in methanol yields the 2-isopropylthiophene (III), which is acetylated with acetyl chloride. Reduction of 2-isopropyl-5-acetylthiophene (IV) with lithium aluminum hydride gives the corresponding alcohol, which is converted to the triphenylphosphonium salt (V). By Wittig reaction with 4-ethoxycarbonyl benzaldehyde (VI) the ethyl ester obtained is then hydrolyzed with potassium hydroxide to yield the free acid.

参考文献中间体

合成目标

【1】 Coquelet, C.; Roussillon, S.; Sincholle, D.; Bonne, C.; Alazet, A. (Chauvin Laboratories SA); New derivatives of 4-vinyl benzoic acid, process for their preparation and their uses in therapeutics ans as ligands. EP 0161156; FR 8405531; US 4929635; WO 8504652 .
【2】 Bonne, C.; Conduzorgues, J.P.; Coquelet, C.; Roussillon, S.; CBS-211 A. Drugs Fut 1986, 11, 7, 557.

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)	24490	1-(2-Thienyl)-1-ethanone; 2-Acetylthiophene	88-15-3	C₆H₆OS	详情	详情
(II)	24491	2-isopropenylthiophene		C₇H₈S	详情	详情
(III)	24492	2-Isopropylthiophene		C₇H₁₀S	详情	详情
(IV)	24493	1-(5-isopropyl-2-thienyl)-1-ethanone		C₉H₁₂OS	详情	详情
(V)	24494	[1-(5-isopropyl-2-thienyl)ethyl](triphenyl)phosphonium bromide		C₂₇H₂₈BrPS	详情	详情
(VI)	24495	ethyl 4-formylbenzoate		C₁₀H₁₀O₃	详情	详情

Extended Information