methyl (E)-3-phenyl-2-propenoate -Drug Synthesis Database

【结构式】

【分子编号】23888

【品名】methyl (E)-3-phenyl-2-propenoate

【CA登记号】103-26-4

【分子式】C₁₀H₁₀O₂

【分子量】162.1882

【元素组成】C 74.06% H 6.21% O 19.73%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

The asymmetric dihydroxylation of methyl cinnamate (I) with AD-alpha reagent in tert-butanol/water gives the (2R,3S)-dihydroxyester (II), which is treated with trimethyl orthobenzoate (III) and TsOH in dichloromethane yielding the benzoate (IV). This compound, without isolation, is treated with acetyl bromide affording (2S,3R)-2-(benzoyloxy)-3-bromo-3-phenylpropionic acid methyl ester (V), which is treated with sodium azide in DMF to give the corresponding (2R,3S)-azido compound (VI). Finally, this compound is reduced with H2 over Pd/C in methanol to the corresponding amine that suffers a benzoyl transposition yielding the target side chain (VII).

参考文献中间体

合成目标

【1】 Hu, Z.; et al.; Utilization of a benzoyl migration to effect an expeditious synthesis of the paclitaxel C-13 side chain. Org Process Res Dev 1997, 1, 5, 387.

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)	23888	methyl (E)-3-phenyl-2-propenoate	103-26-4	C₁₀H₁₀O₂	详情	详情
(II)	38532	methyl (2R,3S)-2,3-dihydroxy-3-phenylpropanoate	122743-18-4	C₁₀H₁₂O₄	详情	详情
(III)	38531	dimethoxy(phenyl)methyl methyl ether; 1-(trimethoxymethyl)benzene	707-07-3	C₁₀H₁₄O₃	详情	详情
(IV)	38533	(1R,2S)-2-hydroxy-1-(methoxycarbonyl)-2-phenylethyl benzoate		C₁₇H₁₆O₅	详情	详情
(V)	38534	(1S,2R)-2-bromo-1-(methoxycarbonyl)-2-phenylethyl benzoate		C₁₇H₁₅BrO₄	详情	详情
(VI)	38535	(1R,2S)-2-azido-1-(methoxycarbonyl)-2-phenylethyl benzoate		C₁₇H₁₅N₃O₄	详情	详情
(VII)	63559	methyl (2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoate	32981-85-4	C₁₇H₁₇NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

2(R),3(S)-Dihydroxy-3-phenylpropionic acid methyl ester, an intermediate in the paclitaxel side chain synthesis, can be prepared by the Sharpless catalytic asymmetric dihydroxylation of methyl cinnamate (I) with K2OsO4, N-methylmorpholine N-oxide (NMO) and a catalytic amount of 1,4-bis(9-O-dihydroquinine)phthalazine [(DHQ)2PHAL] in tert-butanol/water. This reaction has been tested successfully in a 50-kg industrial process.

参考文献中间体

合成目标

【1】 Lu, X.; et al.; Process development of the sharpless catalytic asymmetric dihydroxylation reaction to prepare methyl (2R,3S)-2,3-dihydroxy-3-phenylpropionate. Org Process Res Dev 2000, 4, 6, 575.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	38532	methyl (2R,3S)-2,3-dihydroxy-3-phenylpropanoate	122743-18-4	C₁₀H₁₂O₄	详情	详情
(VII)	23888	methyl (E)-3-phenyl-2-propenoate	103-26-4	C₁₀H₁₀O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

A new synthesis of docetaxel has been developed: The stereoselective dihydroxylation of methyl cinnamate (I) by the Sharpless AD process gives the enantiopure diol (II), which was treated first with tosyl chloride/triethylamine and then with K2CO3 in DMF yielding epoxide (III). Hydrolysis of the ester group of (III) with LiOH in methanol/water affords the epoxy-acid (IV), which is coupled with 7,10-bis(2,2,2-trichloroethoxycarbonyl)-10-deacetylbaccatin III (V) by means of dicyclohexylcarbodiimide (CDD) and dimethylaminopyridine in hot toluene to give the ester (VI). Regioselective cleavage of the epoxide ring of (VI) with NaN3 in aqueous methanol yielded the azide derivative (VII), which was treated with triphenylphosphine in the presence of tert-butoxycarbonyl anhydride and K2CO3 in dichloromethane affording the tert-butoxycarbonylamino derivative (VIII). Finally, (VIII) was submitted to a reductive deprotection with zinc powder in acetic acid.

参考文献中间体

合成目标

【1】 Harada, N.; Yamaguchi, T.; Hashiyama, T.; Ozaki, K.; Synthesis of taxoids 3. A novel and efficient method for preparation of taxoids employing cis-glycidic acid. Tetrahedron Lett 1998, 39, 5575.

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)	23888	methyl (E)-3-phenyl-2-propenoate	103-26-4	C₁₀H₁₀O₂	详情	详情
(II)	23889	methyl (2S,3R)-2,3-dihydroxy-3-phenylpropanoate		C₁₀H₁₂O₄	详情	详情
(III)	23890	methyl (2R,3R)-3-phenyl-2-oxiranecarboxylate	99528-65-1	C₁₀H₁₀O₃	详情	详情
(IV)	23891	(2R,3R)-3-phenyl-2-oxiranecarboxylic acid		C₉H₈O₃	详情	详情
(V)	23892	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₅H₃₈Cl₆O₁₄	详情	详情
(VI)	23893	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (2R,3R)-3-phenyl-2-oxiranecarboxylate		C₄₄H₄₄Cl₆O₁₆	详情	详情
(VII)	23894	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-azido-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl ben		C₄₄H₄₅Cl₆N₃O₁₆	详情	详情
(VIII)	23895	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]		C₄₉H₅₅Cl₆NO₁₈	详情	详情

合成路线4

该中间体在本合成路线中的序号：(XV)

Intermediate (XIV) can be obtained as follows: Bromination of methyl cinnamate (XV) with Br2 in CH2Cl2 provides 2,3-dibromo-3-phenylpropanoate (XVI), which is then converted into alpha-bromocinnamic ester (XVII) by reaction with Et3N in refluxing toluene. Treatment of (XVII) with imidazopyridine (XVIII) and NaH in DMF affords derivative (XIX), which is then hydrolyzed by treatment with NaOH in MeOH to furnish carboxylic acid (XX). Finally, (XX) reacts with carbonylditriazole in DMF to give the target intermediate (XIV).

参考文献中间体

合成目标

【1】 Hemmerle, H.; Schubert, G.; Burger, H.-J.; Herling, A.; Efendic, S. (Aventis SA); Cyclohexane derivs., processes for their preparation and their use as glucose-6-phosphatase inhibitors. CA 2149007; CA 4416433; EP 0682024; JP 1995330767; US 5739147 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIV)	44863			C₁₇H₁₂N₆O	详情	详情
(XV)	23888	methyl (E)-3-phenyl-2-propenoate	103-26-4	C₁₀H₁₀O₂	详情	详情
(XVI)	44865	methyl 2,3-dibromo-3-phenylpropanoate		C₁₀H₁₀Br₂O₂	详情	详情
(XVII)	44866	methyl (Z)-2-bromo-3-phenyl-2-propenoate		C₁₀H₉BrO₂	详情	详情
(XVIII)	44867	1H-imidazo[4,5-b]pyridine		C₆H₅N₃	详情	详情
(XIX)	44868	methyl (Z)-3-(1H-imidazo[4,5-b]pyridin-1-yl)-3-phenyl-2-propenoate		C₁₆H₁₃N₃O₂	详情	详情
(XX)	44869	(Z)-3-(1H-imidazo[4,5-b]pyridin-1-yl)-3-phenyl-2-propenoic acid		C₁₅H₁₁N₃O₂	详情	详情
(XXI)	44870	di(1H-1,2,4-triazol-1-yl)methanone		C₅H₄N₆O	详情	详情

Extended Information