(Z)-3-Phenyl-2-propenoic acid -Drug Synthesis Database

【结构式】

【分子编号】10449

【品名】(Z)-3-Phenyl-2-propenoic acid

【CA登记号】621-82-9

【分子式】C₉H₈O₂

【分子量】148.16132

【元素组成】C 72.96% H 5.44% O 21.6%

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：(III)

A process for the preparation of taxol has been described: The acylation of baccatin III (I) with 2,2,2-trichloroethyl chloroformate in pyridine yields the chloroformate (II), which is acylated with cinnamic acid (III) by means of oxalyl chloride of dicyclohexylcarbodiimide to the cinnamate (IV). The oxidative addition of tert-butyl N-chlorocarbamate (V) to (IV) by means of OsO4 in water affords the protected amino hydroxyester (VI), which is deprotected with iodotrimethylsilane in acetonitrile to give the free aminoester (VII). The benzoylation of (VII) with benzoyl chloride in pyridine affords the protected N-benzoyl derivative (VIII), which is finally deprotected by treatment with Zn and acetic acid to eliminate the trichloroethoxycarbonyl group.

参考文献中间体

合成目标

【1】 Colin, M.; Guenard, D.; Gueritte-Voegelein, F.; Potier, P. (Aventis SA); Process for the preparation of taxol and 10-deacetyltaxol. US 4857653 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
(I)	10447	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₁H₃₈O₁₁	详情	详情
(II)	10448	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₄H₃₉Cl₃O₁₃	详情	详情
(III)	10449	(Z)-3-Phenyl-2-propenoic acid	621-82-9	C₉H₈O₂	详情	详情
(IV)	10450	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-[[(Z)-3-phenyl-2-propenoyl]oxy]-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₃H₄₅Cl₃O₁₄	详情	详情
(VI)	10451	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₈H₅₆Cl₃NO₁₇	详情	详情
(VII)	10452	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[(3-amino-2-hydroxy-3-phenylpropanoyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₃H₄₈Cl₃NO₁₅	详情	详情
(VIII)	10453	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₅₀H₅₂Cl₃NO₁₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The coupling of 2-amino-4-methylthiophene-3-carboxylic acid ethyl ester (I) with N-(tert-butoxycarbonyl)-L-alanine (II) by means of isobutyl chloroformate and NMM, followed by cyclization with triphenylphosphine in CCl4 gives the thieno-oxazinone (III), which is deprotected with TFA yielding (IV) with a free amino group that is acylated with cinnamic acid by means of DEC and DIEA.

参考文献中间体

合成目标

【1】 Tew, D.G.; Pinto, I.L.S.M.; Jarvest, R.L.; Jennings, L.J.; Dabrowski, C.E.; Fernandez, A.V.; Lavery, P.; Inhibition of herpes proteases and antiviral activity of 2-substituted thieno[2,3-d]oxazinones. Bioorg Med Chem Lett 1999, 9, 3, 443.
【2】 Jarvest, R.L.; Jennings, L.J.A.; Pinto, I.L. (SmithKline Beecham plc); Thienoxazinone derivs. useful as antiviral agents. WO 9727200 .

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)	29512	ethyl 2-amino-4-methyl-3-thiophenecarboxylate	43088-42-2	C₈H₁₁NO₂S	详情	详情
(II)	26450	Boc-L-Alanine;(S)-2-((tert-butoxycarbonyl)amino)propanoic acid;N-Boc-L-alanine; (2S)-2-[(tert-butoxycarbonyl)amino]propionic acid	15761-38-3	C₈H₁₅NO₄	详情	详情
(III)	28659	tert-butyl (1S)-1-(5-methyl-4-oxo-4H-thieno[2,3-d][1,3]oxazin-2-yl)ethylcarbamate		C₁₄H₁₈N₂O₄S	详情	详情
(IV)	28660	2-[(1S)-1-aminoethyl]-5-methyl-4H-thieno[2,3-d][1,3]oxazin-4-one		C₉H₁₀N₂O₂S	详情	详情
(V)	10449	(Z)-3-Phenyl-2-propenoic acid	621-82-9	C₉H₈O₂	详情	详情

Extended Information