isopropyl (Z)-3-(4-methoxyphenyl)-2-propenoate -Drug Synthesis Database

【结构式】

【分子编号】62458

【品名】isopropyl (Z)-3-(4-methoxyphenyl)-2-propenoate

【CA登记号】

【分子式】C₁₃H₁₆O₃

【分子量】220.26824

【元素组成】C 70.89% H 7.32% O 21.79%

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：(XXXIX)

The precursor cis-cinnamate (XXXIX) can be obtained by several synthetic routes. Bromination of ethyl trans-4-methoxycinnamate (I) afforded the dibromo ester (XXXVI), which underwent dehydrohalogenation and hydrolysis to the arylpropiolic acid (XXXVII) upon treatment with ethanolic KOH. Acid (XXXVII) was converted to the corresponding isopropyl ester (XXXVIII) by DCC-mediated coupling with isopropanol. Semihydrogenation of (XXXVIII) in the presence of Lindlar catalyst led to the required cis cinnamate (XXXIX). Alternatively, anisaldehyde (X) was converted to the gem-dibromostyrene (XL) by condensation with CBr4 in the presence of PPh3. Reaction of (XL) with BuLi, followed by addition of isopropyl chloroformate to the resultant lithium acetylide, furnished the arylpropiolate (XXXVIII). In another method to obtain the cis-cinnamate (XXXIX), trans-4-methoxycinnamic acid (XLI) was converted to the isopropyl ester (XLII), which was then photochemically isomerized to the desired cis-cinnamate (XXXIX)

参考文献中间体

合成目标

【1】 Jacobsen, E.N.; Deng, L.; Furukawa, Y.; Martinez, L.E.; Enantioselective catalytic epoxidation of cinnamate esters. Tetrahedron 1994, 50, 15, 4323.

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)	62431	ethyl (E)-3-(4-methoxyphenyl)-2-propenoate		C₁₂H₁₄O₃	详情	详情
(X)	27251	4-methoxybenzaldehyde; Anisicaldehyde; p-anisaldehyde	123-11-5	C₈H₈O₂	详情	详情
(XXXVI)	62454	ethyl 2,3-dibromo-3-(4-methoxyphenyl)propanoate		C₁₂H₁₄Br₂O₃	详情	详情
(XXXVII)	62455	3-(4-methoxyphenyl)-2-propynoic acid		C₁₀H₈O₃	详情	详情
(XXXVIII)	62457	isopropyl 3-(4-methoxyphenyl)-2-propynoate		C₁₃H₁₄O₃	详情	详情
(XXXIX)	62458	isopropyl (Z)-3-(4-methoxyphenyl)-2-propenoate		C₁₃H₁₆O₃	详情	详情
(XL)	62456	1-(2,2-dibromovinyl)-4-methoxybenzene; 4-(2,2-dibromovinyl)phenyl methyl ether		C₉H₈Br₂O	详情	详情
(XLI)	42108	(E)-3-(4-methoxyphenyl)-2-propenoic acid	830-09-1	C₁₀H₁₀O₃	详情	详情
(XLII)	63416	isopropyl (E)-3-(4-methoxyphenyl)-2-propenoate		C₁₃H₁₆O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXXIX)

The key cis glycidate ester (XLIII) was prepared by (salen)Mn(III)-catalyzed asymmetric epoxidation of the cis cinnamate (XXXIX). Epoxide opening in (XLIII) with 2-nitrothiophenol (XLIV), with inversion of the configuration, led to the nitro ester adduct (XLV). The nitro group of (XLV) was then reduced to the aniline derivative (XLVI) by means of FeSO4. Subsequent isopropyl ester group saponification in (XLVI) furnished amino acid (XXIX). This was then cyclized to the target thiazepinone (VIII) in refluxing xylene

参考文献中间体

合成目标

【1】 Jacobsen, E.N.; Deng, L.; Furukawa, Y.; Martinez, L.E.; Enantioselective catalytic epoxidation of cinnamate esters. Tetrahedron 1994, 50, 15, 4323.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	62502	4-Picoline N-oxide; 4-Methyl-1-pyridiniumolate	1003-67-4	C₆H₇NO	详情	详情
(VIII)	62436	(2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one		C₁₆H₁₅NO₃S	详情	详情
(XXIX)	62448	(2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid		C₁₆H₁₇NO₄S	详情	详情
(XXXIX)	62458	isopropyl (Z)-3-(4-methoxyphenyl)-2-propenoate		C₁₃H₁₆O₃	详情	详情
(XLIII)	62459	isopropyl (2R,3R)-3-(4-methoxyphenyl)-2-oxiranecarboxylate		C₁₃H₁₆O₄	详情	详情
(XLIV)	62460	2-nitrobenzenethiol; 2-nitrophenylhydrosulfide		C₆H₅NO₂S	详情	详情
(XLV)	62461	isopropyl (2S,3S)-2-hydroxy-3-(4-methoxyphenyl)-3-[(2-nitrophenyl)sulfanyl]propanoate		C₁₉H₂₁NO₆S	详情	详情
(XLVI)	62462	isopropyl (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoate		C₁₉H₂₃NO₄S	详情	详情

Extended Information