4-(4-fluorophenyl)-4-oxobutyric acid -Drug Synthesis Database

【结构式】

【分子编号】39863

【品名】4-(4-fluorophenyl)-4-oxobutyric acid

【CA登记号】366-77-8

【分子式】C₁₀H₉FO₃

【分子量】196.1780632

【元素组成】C 61.22% H 4.62% F 9.68% O 24.47%

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：(A)

The condensation of (VIII) with 3-(p-fluorobenzoyl)propionic acid (A) by means of ethyl chloroformate (B) and triethylamine in CHCl3 gives the corresponding N,O-diacyl derivative (X), which is then reduced with LiAlH4 in refluxing THF yielding 5,9-dimethyl-2-[4''-(p-fluorophenyl)4''-hydroxy-1''-butyl]-2'-hydroxy-5,9-dimethyl-6,7-benzomorphane (XI). Finally, this compound is oxidized with Jones reagent (H2CrO4 in H2SO4).

参考文献中间体

合成目标

【1】 Atsumi, T.; et al. (Sumitomo Chemical Co., Ltd.); Processes for producing 2-benzoylalkylbenzomorphan derivatives and their salts. DE 2114511; ES 389920; FR 2092005; GB 1311387 .
【2】 Castaner, J.; Paton, D.M.; ID-1229. Drugs Fut 1978, 3, 4, 298.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	11229	1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate	541-41-3	C₃H₅ClO₂	详情	详情
(A)	39863	4-(4-fluorophenyl)-4-oxobutyric acid	366-77-8	C₁₀H₉FO₃	详情	详情
(VIII)	36016	(1R,9R,13R)-1,13-dimethyl-10-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-trien-4-ol		C₁₄H₁₉NO	详情	详情
(X)	39864	(1R,9R,13R)-10-[4-(4-fluorophenyl)-4-oxobutanoyl]-1,13-dimethyl-10-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-trien-4-yl 4-(4-fluorophenyl)-4-oxobutanoate		C₃₄H₃₃F₂NO₅	详情	详情
(XI)	39865	(1R,9R,13R)-10-[4-(4-fluorophenyl)-4-hydroxybutyl]-1,13-dimethyl-10-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-trien-4-ol		C₂₄H₃₀FNO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Reduction of 3-(4-fluorobenzoyl)propionic acid (I) by means of AlCl3 in CH2Cl2 and borane/tert-butylamine complex yields alcohol (II), which is then converted into aldehyde (IV) by reaction with 4-hydroxybenzaldehyde (III) in presence of PPh3 in THF and diethyl azodicarboxylate. Treatment of (IV) with a solution of methyltriphenylphosphonium bromide in THF and a solution of n-BuLi in hexane affords styrene derivative (V), which couples with 2’-hydroxy-3’-iodoacetophenone (VI) in presence of Et3N and Pd(OAc)2 in CH3CN to provide (VII). Cyclization of (VII) by means of a first treatment with NaOEt in EtOH followed by reaction with diethyl oxalate in Et2O/EtOH yields benzopyrane derivative (VIII) which is then hydrolyzed with NaOH in THF/MeOH to give (IX). Carboxylic acid (IX) is first converted into carboxamide (X) by treatment with a saturated NH3 solution in MeOH and then into carbonitrile (XI) by means of POCl3 in DMF. Finally, treatment of (XI) with a solution of NaN3, NH4Cl and DMF leads to the formation of the desired product.

参考文献中间体

合成目标

【1】 Carganico, G.; Mauleon Casellas, D.; Pascual Avellana, J.; Garcia Perez, M.L.; Palomer Benet, A. (Menarini Industrie Farma Riunite srl); Benzopyran derivs. having leukotriene-antagonistic action. EP 0888327; ES 2127106; JP 2000506878; US 5990142; WO 9734885 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	17571	Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate	95-92-1	C₆H₁₀O₄	详情	详情
(A)	30484	Methyl(triphenyl)phosphonium bromide	1779-49-3	C₁₉H₁₈BrP	详情	详情
(I)	39863	4-(4-fluorophenyl)-4-oxobutyric acid	366-77-8	C₁₀H₉FO₃	详情	详情
(II)	41474	4-(4-fluorophenyl)-1-butanol		C₁₀H₁₃FO	详情	详情
(III)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(IV)	41475	4-[4-(4-fluorophenyl)butoxy]benzaldehyde		C₁₇H₁₇FO₂	详情	详情
(V)	41476	1-fluoro-4-[4-(4-vinylphenoxy)butyl]benzene; 4-(4-fluorophenyl)butyl 4-vinylphenyl ether		C₁₈H₁₉FO	详情	详情
(VI)	27290	1-(2-hydroxy-3-iodophenyl)-1-ethanone		C₈H₇IO₂	详情	详情
(VII)	41477	1-[3-((E)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl)-2-hydroxyphenyl]-1-ethanone		C₂₆H₂₅FO₃	详情	详情
(VIII)	41478	ethyl 8-((E)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl)-4-oxo-4H-chromene-2-carboxylate		C₃₀H₂₇FO₅	详情	详情
(IX)	41479	8-((E)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl)-4-oxo-4H-chromene-2-carboxylic acid		C₂₈H₂₃FO₅	详情	详情
(X)	41480	8-((E)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl)-4-oxo-4H-chromene-2-carboxamide		C₂₈H₂₄FNO₄	详情	详情
(XI)	41481	8-((E)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl)-4-oxo-4H-chromene-2-carbonitrile		C₂₈H₂₂FNO₃	详情	详情

Extended Information