ethyl 3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propanoate -Drug Synthesis Database

【结构式】

【分子编号】27001

【品名】ethyl 3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propanoate

【CA登记号】

【分子式】C₂₀H₂₄FNO₂

【分子量】329.4145032

【元素组成】C 72.92% H 7.34% F 5.77% N 4.25% O 9.71%

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：(XIV)

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

合成路线2

该中间体在本合成路线中的序号：(XI)

The reaction of 3-bromo-5-iodobenzoic acid (I) with SOCl2 gives the corresponding acyl chloride (II), which by a Friedel-Crafts condensation with fluorobenzene (II) by means of AlCl3 in refluxing dichloromethane yields the benzophenone (IV). The condensation of (IV) with ethyl acrylate (V) by means of palladium acetate and triethylamine in refluxing acetonitrile affords the cinnamic acid derivative (VI), which is condensed with N-vinylphthalimide (VII) by means of palladium acetate and diisopropylamine in refluxing xylene to provide the unsaturated adduct (VIII). The reduction of the carbonyl group of (VIII) with triethylsilane and TFA gives the diphenylmethane derivative (IX), which is hydrogenated with H2 over Pd/C in ethyl acetate to yield the saturated diphenylmethane derivative (X). Elimination of the phthalimido group of (X) with hydrazine affords (XI) with a primary amino group. that is sulfonated with 4-chlorophenylsulfonyl chloride (XII) and triethylamine in THF to provide the sulfonamide (XIII). Finally, the ester group of (XIII) is hydrolyzed with aqueous NaOH.

参考文献中间体

合成目标

【1】 Waite, D.C.; Mason, C.P.; A scalable synthesis of the thromboxane receptor antagonist 3-(3-[2-(4-chlorobenzenesulfonamido)ethyl]-5-(4-fluorobenzyl)phenyl]propionic acid via a regioselective heck cross-coupling strategy. Org Process Res Dev 1998, 2, 2, 116.

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)	32745	3-bromo-5-iodobenzoic acid	188815-32-9	C₇H₄BrIO₂	详情	详情
(II)	32746	3-bromo-5-iodobenzoyl chloride		C₇H₃BrClIO	详情	详情
(III)	17466	Fluorobenzene	462-06-6	C₆H₅F	详情	详情
(IV)	32747	(3-bromo-5-iodophenyl)(4-fluorophenyl)methanone		C₁₃H₇BrFIO	详情	详情
(V)	10164	ethyl acrylate	140-88-5	C₅H₈O₂	详情	详情
(VI)	32748	ethyl (E)-3-[3-bromo-5-(4-fluorobenzoyl)phenyl]-2-propenoate		C₁₈H₁₄BrFO₃	详情	详情
(VII)	32749	2-vinyl-1H-isoindole-1,3(2H)-dione	3485-84-5	C₁₀H₇NO₂	详情	详情
(VIII)	32750	ethyl (E)-3-[3-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]-5-(4-fluorobenzoyl)phenyl]-2-propenoate		C₂₈H₂₀FNO₅	详情	详情
(IX)	32751	ethyl (E)-3-[3-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]-5-(4-fluorobenzyl)phenyl]-2-propenoate		C₂₈H₂₂FNO₄	详情	详情
(X)	32752	ethyl 3-[3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4-fluorobenzyl)phenyl]propanoate		C₂₈H₂₆FNO₄	详情	详情
(XI)	27001	ethyl 3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propanoate		C₂₀H₂₄FNO₂	详情	详情
(XII)	15787	4-chlorobenzenesulfonyl chloride;4-chlorobenzene-1-sulfonyl chloride	98-60-2	C₆H₄Cl₂O₂S	详情	详情
(XIII)	27002	ethyl 3-[3-(2-[[(4-chlorophenyl)sulfonyl]amino]ethyl)-5-(4-fluorobenzyl)phenyl]propanoate		C₂₆H₂₇ClFNO₄S	详情	详情

Extended Information