3-[3-(3-ethoxy-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propionic acid -Drug Synthesis Database

【结构式】

【分子编号】26996

【品名】3-[3-(3-ethoxy-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propionic acid

【CA登记号】

【分子式】C₂₁H₂₃FO₄

【分子量】358.4096232

【元素组成】C 70.38% H 6.47% F 5.3% O 17.86%

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：(VIII)

The reaction of 1,3,5-tribromobenzene (I) with 4-fluorobenzaldehyde (II) by means of BuLi in ethyl ether gives the benzhydrol (III), which is condensed with ethyl acrylate (IV) by means of palladium acetate and tri o-tolylphosphine in refluxing acetonitrile yielding the phenylenebisacrylate (V). The acetylation of (V) with acetic anhydride and DMAP in dichloromethane affords the acetate (VI), which is hydrogenated with H2 over Pd/C in ethyl acetate providing the bispropanoate (VII). Selective hydrolysis of (VII) with NaOH in ethanol gives the monoacid (VIII), which is treated with oxalyl chloride in dichloromethane yielding the monoacyl chloride (IX). The reaction of (IX) with NH4OH affords the corresponding amide (X), which is treated with NaOCl and NaOH to perform degradation of the amide group and simultaneous hydrolysis of the ester group providing the amino acid (XI). Finally, this compound is sulfonated with 4-chlorophenylsulfonyl chloride (XII) and NaOH.

参考文献中间体

合成目标

【1】 Dack, K.N.; Dickinson, R.P.; Long, C.J.; Steele, J.; Thromboxane modulating agents. 4. Design and synthesis of 3-(2-[((4-chlorophenyl)sulfonyl)amino]ethyl)benzenepropanoic acid derivatives as potent thromboxane receptor antagonists. Bioorg Med Chem Lett 1998, 8, 16, 2061.

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)	26991	1,3,5-tribromobenzene	626-39-1	C₆H₃Br₃	详情	详情
(II)	12337	4-fluorobenzaldehyde	459-57-4	C₇H₅FO	详情	详情
(III)	26992	(3,5-dibromophenyl)(4-fluorophenyl)methanol		C₁₃H₉Br₂FO	详情	详情
(IV)	10164	ethyl acrylate	140-88-5	C₅H₈O₂	详情	详情
(V)	26993	ethyl (E)-3-[3-[(E)-3-ethoxy-3-oxo-1-propenyl]-5-[(4-fluorophenyl)(hydroxy)methyl]phenyl]-2-propenoate		C₂₃H₂₃FO₅	详情	详情
(VI)	26994	ethyl (E)-3-[3-[(acetoxy)(4-fluorophenyl)methyl]-5-[(E)-3-ethoxy-3-oxo-1-propenyl]phenyl]-2-propenoate		C₂₅H₂₅FO₆	详情	详情
(VII)	26995	ethyl 3-[3-(3-ethoxy-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propanoate		C₂₃H₂₇FO₄	详情	详情
(VIII)	26996	3-[3-(3-ethoxy-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propionic acid		C₂₁H₂₃FO₄	详情	详情
(IX)	26997	ethyl 3-[3-(3-chloro-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propanoate		C₂₁H₂₂ClFO₃	详情	详情
(X)	26998	ethyl 3-[3-(3-amino-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propanoate		C₂₁H₂₄FNO₃	详情	详情
(XI)	26999	3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propionic acid		C₁₈H₂₀FNO₂	详情	详情
(XII)	15787	4-chlorobenzenesulfonyl chloride;4-chlorobenzene-1-sulfonyl chloride	98-60-2	C₆H₄Cl₂O₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The reaction of monoacid (VIII) with diphenylphosphoryl azide and triethylamine in refluxing tert-butanol gives the tert-butoxycarbonyl aminoester (XIII), which is deprotected with trifluoroacetic acid to yield the aminoester (XIV). The sulfonation of (XIV) with 4-chlorophenylsulfonyl chloride (XII) and triethylamine in dichloromethane affords the sulfonamido ester (XV), which is finally hydrolyzed with NaOH in refluxing methanol.

参考文献中间体

合成目标

【1】 Dickinson, R.P.; Dack, K.N.; Steele, J. (Pfizer Inc.); Benzenealkanoic acids for cardiovascular diseases. EP 0662950; JP 1996502046; US 5618941; WO 9406761 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	26996	3-[3-(3-ethoxy-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propionic acid		C₂₁H₂₃FO₄	详情	详情
(XII)	15787	4-chlorobenzenesulfonyl chloride;4-chlorobenzene-1-sulfonyl chloride	98-60-2	C₆H₄Cl₂O₂S	详情	详情
(XIII)	27000	ethyl 3-[3-[2-[(tert-butoxycarbonyl)amino]ethyl]-5-(4-fluorobenzyl)phenyl]propanoate		C₂₅H₃₂FNO₄	详情	详情
(XIV)	27001	ethyl 3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propanoate		C₂₀H₂₄FNO₂	详情	详情
(XV)	27002	ethyl 3-[3-(2-[[(4-chlorophenyl)sulfonyl]amino]ethyl)-5-(4-fluorobenzyl)phenyl]propanoate		C₂₆H₂₇ClFNO₄S	详情	详情

Extended Information