methyl 3-phenylpropanoate -Drug Synthesis Database

【结构式】

【分子编号】23523

【品名】methyl 3-phenylpropanoate

【CA登记号】103-25-3

【分子式】C₁₀H₁₂O₂

【分子量】164.20408

【元素组成】C 73.15% H 7.37% O 19.49%

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：(II)

This compound can be obtained by two different ways: 1) The Friedel Crafts' condensation of trans-4-aminomethylcyclohexylcarbonyl chloride (I) with methyl 3-phenylpropionate (II) by means of AlCl3 in refluxing S2C gives methyl 3-[4-trans-4-aminomethylcyclohexylcarbonyl)phenyl]propionate (III), which is then hydrolyzed with hot aqueous concentrated HCl. 2) By isomerization of 3-[4-(cis-4-aminomethylcyclohexylcarbonyl)phenyl]propionic acid (IV) in hot aqueous 3N HCl.

参考文献中间体

合成目标

【1】 Verloes, R.; Delire, M.; Brichard, V.; Portielje, J.P.; Stoter, G.; Kruit, W.H.J.; van Ojik, H.H.; Drugs Today 1980, 16, 9, 290.
【2】 Takeshita, T.; Hoshina, K.; Ohtsu, A.; Naruchi, T. (Teijin Ltd.); Aminocarboxylic acids, amino alcohols or the derivatives thereof, processes for production thereof and pharmaceutical uses thereof. CA 1176267; EP 0044541; US 4402975 .
【3】 Castaner, J.; Serradell, M.N.; TEI-5103. Drugs Fut 1985, 10, 6, 485.

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)	29709	4-(aminomethyl)cyclohexanecarbonyl chloride		C₈H₁₄ClNO	详情	详情
(II)	23523	methyl 3-phenylpropanoate	103-25-3	C₁₀H₁₂O₂	详情	详情
(III)	29710	methyl 3-(4-[[4-(aminomethyl)cyclohexyl]carbonyl]phenyl)propanoate		C₁₈H₂₅NO₃	详情	详情
(IV)	29711	3-(4-[[4-(aminomethyl)cyclohexyl]carbonyl]phenyl)propionic acid		C₁₇H₂₃NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

This compound can be prepared by two related ways: 1) The condensation of isatin (I) with methyl 3-phenylpropionate (II) by means of lithium diisopropylamide (LDA) in THF gives methyl alpha-benzyl-3 hydroxy-2-oxo-2,3-dihydro-1H-indole-3-acetate (III), which is reduced with LiAlH4 in THF to afford beta-benzylindole-3-ethanol (IV). The cyclization of (IV) with methyl propionylacetate (V) by means of boron trifluoride ethearate to toluene yields methyl 4-benzyl-1-ethyl 1,3,4,9 tetrahydropyrano[3,4-b]indole-1-acetate (VI), which is finally hydrolyzed with NaOH in refluxing ethanol. 2) The alkylation of methyl indole-3-acetate (VII) with benzyl chloride (VIII) by means of LDA o THF gives methyl alpha-benzylindole-3-acetate (IX), which is reduced with LiAlH4 in THF to the alcohol (IV), already obtained.

参考文献中间体

合成目标

【1】 Gavin, G.; Katz, A.H.; Conway, K.M.; Asselin, A.A.; Demerson, C.A.; Guinoso, C.; Shah, V.; Mobilio, D.; Noureldin, R.; Humber, L.G.; Chau, T.T.; Jensen, N.P.; Schimid, J.; Shaw, C.-C.; Weichman, B.M.; Van Engen, D.; Synthesis and analgesic activity of pemedolac (cis. J Med Chem 1988, 31, 6, 1244.
【2】 Katz, A.H.; Demerson, C.A.; Humber, L.G. (American Home Products Corp.); Substd. 1,3,4,9-tetrahydropyrano[3,4-b]indole-1-ac. EP 0238226; JP 1987221688; US 4670462; US 4775690 .
【3】 Castaner, J.; Prous, J.; Pemedolac. Drugs Fut 1988, 13, 9, 834.

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)	14098	2,3-Indolinedione; 1H-Indole-2,3-dione; Isatin	91-56-5	C₈H₅NO₂	详情	详情
(II)	23523	methyl 3-phenylpropanoate	103-25-3	C₁₀H₁₂O₂	详情	详情
(III)	23524	methyl 2-(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-3-phenylpropanoate		C₁₈H₁₇NO₄	详情	详情
(IV)	23525	2-(1H-indol-3-yl)-3-phenyl-1-propanol		C₁₇H₁₇NO	详情	详情
(V)	15536	methyl 3-oxopentanoate	30414-53-0	C₆H₁₀O₃	详情	详情
(VI)	23527	methyl 2-(4-benzyl-1-ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetate		C₂₃H₂₅NO₃	详情	详情
(VII)	23528	2-(1H-Indol-3-yl)acetic acid methyl ester	1912-33-0	C₁₁H₁₁NO₂	详情	详情
(VIII)	19171	1-(Chloromethyl)benzene; Benzyl chloride	100-44-7	C₇H₇Cl	详情	详情
(IX)	23529	methyl 2-(1H-indol-3-yl)-3-phenylpropanoate		C₁₈H₁₇NO₂	详情	详情

Extended Information