methyl 2-phenylacetate -Drug Synthesis Database

【结构式】

【分子编号】32831

【品名】methyl 2-phenylacetate

【CA登记号】101-41-7

【分子式】C₉H₁₀O₂

【分子量】150.1772

【元素组成】C 71.98% H 6.71% O 21.31%

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)

Condensation of 2-nitrobenzaldehyde (I) with methyl phenylacetate (II) in the presence of lithium diisopropylamide in cold THF provided hydroxyester (III). Reduction of the nitro group of (III) with concomitant cyclization by hydrogenation over Pd/C in EtOAc produced the dihydroquinolinone (IV). Further hydrogenolysis of the hydroxyl group of (IV) over Pd/C in AcOH gave (V), which was finally alkylated with benzyl bromide and NaH to yield the N-benzylquinolinone.

参考文献中间体

合成目标

【1】 Cho, W.-J.; Lee, J.Y.; Chung, B.-H.; Kim, T.S.; Choi, B.-G.; Cheon, S.H.; Studies on the synthesis and in vitro antitumor activity of the isoquinolone derivatives. Arch Pharmacal Res 1999, 22, 2, 179.

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)	11370	2-Nitrobenzaldehyde	552-89-6	C₇H₅NO₃	详情	详情
(II)	32831	methyl 2-phenylacetate	101-41-7	C₉H₁₀O₂	详情	详情
(III)	32832	methyl 3-hydroxy-3-(2-nitrophenyl)-2-phenylpropanoate		C₁₆H₁₅NO₅	详情	详情
(IV)	32833	4-hydroxy-3-phenyl-3,4-dihydro-2(1H)-quinolinone		C₁₅H₁₃NO₂	详情	详情
(V)	32834	3-phenyl-3,4-dihydro-2(1H)-quinolinone		C₁₅H₁₃NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Michael addition of methyl acrylate (VIII) to methyl phenylacetate (VII) in the presence of NaH produces the intermediate triester (IX) which, under the reaction conditions, undergoes Dieckmann cyclization to the cyclohexanone diester (X). Hydrolysis and decarboxylation of keto diester (X) leads to keto acid (XI). This is then subjected to Curtius rearrangement in the presence of diphenylphosphoryl azide (DPPA) to yield, after acidic hydrolysis of the intermediate isocyanate, the amino cyclohexanone (XII). Acylation of amine (XII) by acid chloride (VI) then gives amide (XIII).

参考文献中间体

合成目标

【1】 Elliott, J.M.; Castro Pineiro, J.L.; Swain, C.J.; Hollingworth, G.J.; Dinnell, K.; Shaw, D.E. (Merck Sharp & Dohme Ltd.); Cyclohexane derivs. and their use as therapeutic agents. WO 0187838 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	57084	2-[3,5-bis(trifluoromethyl)phenyl]propanoyl chloride		C₁₁H₇ClF₆O	详情	详情
(VII)	32831	methyl 2-phenylacetate	101-41-7	C₉H₁₀O₂	详情	详情
(VIII)	14156	methyl acrylate	96-33-3	C₄H₆O₂	详情	详情
(IX)	57085	trimethyl 3-phenyl-1,3,5-pentanetricarboxylate		C₁₇H₂₂O₆	详情	详情
(X)	57086	dimethyl 4-oxo-1-phenyl-1,3-cyclohexanedicarboxylate		C₁₆H₁₈O₅	详情	详情
(XI)	57087	4-oxo-1-phenylcyclohexanecarboxylic acid		C₁₃H₁₄O₃	详情	详情
(XII)	57088	4-amino-4-phenylcyclohexanone		C₁₂H₁₅NO	详情	详情
(XIII)	57089	2-[3,5-bis(trifluoromethyl)phenyl]-N-(4-oxo-1-phenylcyclohexyl)propanamide		C₂₃H₂₁F₆NO₂	详情	详情

Extended Information