Cinnamic acid ethylester; Ethyl cinnamate -Drug Synthesis Database

【结构式】

【分子编号】54905

【品名】Cinnamic acid ethylester; Ethyl cinnamate

【CA登记号】

【分子式】C₁₁H₁₂O₂

【分子量】176.21508

【元素组成】C 74.98% H 6.86% O 18.16%

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：(I)

The asymmetric dihydroxylation of trans-cinnamic acid ethyl ester (I) with AD mix alpha gives (2R,3S)-2,3-dihydroxy-3-phenylpropionic acid ethyl ester (II), which is submitted to the cyclic iminocarbonate rearrangement protocol with Bu4SnO, PhCO-NCS and MgI2 to yield the chiral oxazolidinone (III). The hydrolysis of (III) in refluxing 10% HCl affords (2R,3S)-3-amino-2-hydroxy-3-phenylpropionic acid (IV), which is finally N-benzoylated by means of benzoyl chloride and NaOH to provide the target side chain acid (V).

参考文献中间体

合成目标

【1】 Cho, G.Y.; et al.; Improving the regioselectivity in the cyclic iminocarbonate rearrangement: Enantioselective synthesis of the paclitaxel side chain. Bull Korean Chem Soc 2001, 22, 4, 432.

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)	54905	Cinnamic acid ethylester; Ethyl cinnamate		C₁₁H₁₂O₂	详情	详情
(II)	54906	ethyl (2R,3S)-2,3-dihydroxy-3-phenylpropanoate		C₁₁H₁₄O₄	详情	详情
(III)	54907	ethyl (4S,5R)-3-benzoyl-2-oxo-4-phenyl-1,3-oxazolidine-5-carboxylate		C₁₉H₁₇NO₅	详情	详情
(IV)	54908	(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoic acid	136561-53-0	C₉H₁₁NO₃	详情	详情
(V)	31988	(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropionic acid		C₁₆H₁₅NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

In the original synthesis of the title compound, Knoevenagel condensation of benzaldehyde (I) with malonic acid (II) in the presence of ammonium acetate produced the beta-aminoacid (III). Reductive alkylation of the amino group of (III) with formaldehyde produced the dimethyl amine (IV). Then, Fischer esterification of (IV) with ethanolic HCl furnished the intermediate amino ester (V). Amino ester (V) was alternatively obtained by Michael addition of dimethylamine to ethyl cinnamate (VI). Reduction of the ester function of (V) provided amino alcohol (VII). The sodium alkoxide of (VII) was then coupled with 1-fluoronaphthalene (VIII) to produce the racemic amino ether, which was finally resolved into enantiomers by means of tartaric acid.

参考文献中间体

合成目标

【1】 Robertson, D.W.; Thompson, D.C.; Wong, D.T. (Eli Lilly and Company); 1-Phenyl-3-naphthalenyloxypropanamines. AU 8814335; EP 0288188; JP 1988258837; US 5135947 .
【2】 Wheeler, W.J.; O'Bannon, D.D.; A chiral synthesis of dapoxetine hydrochloride, a serotonin reuptake inhibitor, and its 14C isotopomer. J Label Compd Radiopharm 1992, 31, 4, 305.

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)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(II)	12963	Malonic acid	141-82-2	C₃H₄O₄	详情	详情
(III)	59224	3-(3-Aminophenyl)propionic acid; beta-Aminohydrocinnamic acid; DL-3-Amino-3-phenylpropionic acid; 3-Amino-3-phenylpropionic acid	614-19-7	C₉H₁₁NO₂	详情	详情
(IV)	59221	N,N-dimethyl-3-phenyl-beta-alanine		C₁₁H₁₅NO₂	详情	详情
(V)	59222	ethyl 3-(dimethylamino)-3-phenylpropanoate		C₁₃H₁₉NO₂	详情	详情
(VI)	54905	Cinnamic acid ethylester; Ethyl cinnamate		C₁₁H₁₂O₂	详情	详情
(VII)	59223	3-(dimethylamino)-3-phenyl-1-propanol		C₁₁H₁₇NO	详情	详情
(VIII)	40503	1-fluoronaphthalene	321-38-0	C₁₀H₇F	详情	详情

Extended Information