2-Diazoacetic acid ethyl ester -Drug Synthesis Database

【结构式】

【分子编号】31205

【品名】2-Diazoacetic acid ethyl ester

【CA登记号】

【分子式】C₄H₆N₂O₂

【分子量】114.10392

【元素组成】C 42.11% H 5.3% N 24.55% O 28.04%

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：(V)

Felbinac ethyl can be obtained in two different ways: 1) The Friedel-Craft's condensation of 2-chloro-2-(methylthio)acetic acid ethyl ester (I) with biphenyl (II) by means of SnCl4 in dichloromethane gives 2-(methylthio)-4-biphenylylacetic acid ethyl ester (III), which is reduced with Zn in acetic acid. 2) By condensation of diazoacetic acid ethyl ester (V) with 4-biphenylyldichloroborane (VI) in THF.

参考文献中间体

合成目标

【1】 Purcell, T.A.; Rivron, L.; Zard, L. (Sanofi-Synthelabo ); Method for the preparation of 4-biphenylacetic acids. AU 8782884; EP 0272981; FR 2608206; JP 1988185975; US 4810723 .
【2】 Hooz, J.; Bridson, J.N.; Calzada, J.G.; Brown, H.C.; Midland, M.M.; Levy, A.B.; The reaction of alkyl- and aryldichloroboranes with ethyl diazoacetate at low temperature. J Org Chem 1973, 38, 14, 2574-76.
【3】 Prous, J.; Castaner, J.; LM-001. Drugs Fut 1990, 15, 11, 1077.

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)	31202	1,1'-biphenyl	92-52-4	C₁₂H₁₀	详情	详情
(II)	21726	ethyl 2-chloro-2-(methylsulfanyl)acetate		C₅H₉ClO₂S	详情	详情
(III)	31203	ethyl 2-[1,1'-biphenyl]-4-yl-2-(methylsulfanyl)acetate		C₁₇H₁₈O₂S	详情	详情
(IV)	31204	4-(dichloroboryl)-1,1'-biphenyl		C₁₂H₉BCl₂	详情	详情
(V)	31205	2-Diazoacetic acid ethyl ester		C₄H₆N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The chiral dihydroxypentenal acetonide (II) is obtained from D-ribose (I) by known methods. The condensation of (II) with ethyl diazoacetate (III) by means of SnCl2 in dichloromethane gives diazocompound (IV), which is submitted to an intramolecular cyclopropanation by means of Ts-N3 and CuI in refluxing toluene to afford the bicyclo[3,1,0] hexane derivative (V). The reduction of the ketone and ester groups of (V) by means of LiAlH4 in ethyl ether provides the bicyclo diol (VI), which is deprotected with HCl in THF/water to give the chiral tetrol (VII). Selective protection of the primary OH group of (VII) with trityl chloride, TEA and DMAP in DMF yields the trityl ether (VIII), which is oxidized with NaIO4 in THF/water to afford tritylated (1S,2R)-1,2-bis(hydroxymethyl)cyclopropanemethanol (IX). The acylation of (IX) with benzoyl chloride and pyridine provides the tritylated diester (X), which is finally deprotected with formic acid in ethyl ether to furnish the target intermediate (1S,2R)-bis(benzoyloxy)cyclopropanemethanol (XI) (see intermediate (XI) in scheme no. 19209002a of the current synthesis).

参考文献中间体

合成目标

【1】 Gallos, J.K.; et al.; Carbocyclic nucleoside precursors by intramolecular cyclopropanation of sugar-derived diazo compounds. Tetrahedron Lett 2001, 42, 42, 7489.

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)	53933	beta-D-ribofuranose		C₅H₁₀O₅	详情	详情
(II)	53934	(4R,5R)-2,2-dimethyl-5-vinyl-1,3-dioxolane-4-carbaldehyde	n/a	C₈H₁₂O₃	详情	详情
(III)	31205	2-Diazoacetic acid ethyl ester		C₄H₆N₂O₂	详情	详情
(IV)	53935			C₁₂H₁₆N₂O₅	详情	详情
(V)	53936	ethyl (3aR,3bR,5aR)-2,2-dimethyl-5-oxotetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-4a(3aH)-carboxylate		C₁₂H₁₆O₅	详情	详情
(VI)	53937	(3aR,3bR,4aS,5S,5aS)-4a-(hydroxymethyl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-ol		C₁₀H₁₆O₄	详情	详情
(VII)	53938	(1S,2S,3R,4R,5R)-1-(hydroxymethyl)bicyclo[3.1.0]hexane-2,3,4-triol		C₇H₁₂O₄	详情	详情
(VIII)	53939	(1S,2S,3R,4R,5R)-1-[(trityloxy)methyl]bicyclo[3.1.0]hexane-2,3,4-triol		C₂₆H₂₆O₄	详情	详情
(IX)	53940	{(1R,2R)-2-(hydroxymethyl)-2-[(trityloxy)methyl]cyclopropyl}methanol		C₂₅H₂₆O₃	详情	详情
(X)	53941	{(1R,2S)-2-[(benzoyloxy)methyl]-2-[(trityloxy)methyl]cyclopropyl}methyl benzoate		C₃₉H₃₄O₅	详情	详情
(XI)	53929	[(1R,2S)-2-[(benzoyloxy)methyl]-2-(hydroxymethyl)cyclopropyl]methyl benzoate		C₂₀H₂₀O₅	详情	详情

Extended Information