　 -Drug Synthesis Database

【结构式】

【分子编号】58942

【品名】　

【CA登记号】

【分子式】C₁₀H₁₀LiNO₂

【分子量】183.13594

【元素组成】C 65.59% H 5.5% Li 3.79% N 7.65% O 17.47%

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：(XV)

In a different procedure, 3,4-dichlorophenylacetic acid (XIV) was condensed with the lithiated chiral oxazolidinone (XV), via activation as the mixed anhydride with pivaloyl chloride, to afford the N-acyl oxazolidinone (XVI). Diastereoselective alkylation of the sodium enolate of (XVI) with allyl iodide (XVII) afforded the (S)-pentenyl oxazolidinone (XVIII), which was further hydrolyzed to the chiral acid (XIX) by means of lithium peroxide. Alternatively, acid (XIX) was obtained by alkylation of the lithium dianion of 3,4-dichlorophenylacetic acid (XIV) with allyl bromide (XX), followed by resolution of the resultant racemic acid (XXI) with (S)-1-phenylethylamine. Acid (XIX) was converted to the amide (XXII) via the corresponding acid chloride. Reduction of amide (XXII) with DIBAL gave the secondary amine (XXIII), which was subsequently acylated with benzoyl chloride, yielding benzamide (XXIV). Dihydroxylation of the olefin double bond with N-methylmorpholine-N-oxide in the presence of OsO4, followed by oxidative cleavage of the resultant diol (XXV) with sodium periodate furnished aldehyde (XXVI). Finally, reductive amination of aldehyde (XXVI) with piperidine (III) in the presence of NaBH3CN provided the title compound

参考文献中间体

合成目标

【1】 Hale, J.J.; Finke, P.E.; MacCross, M.; A facile synthesis of the novel neurokinin A antagonist SR 48968. Bioorg Med Chem Lett 1993, 3, 2, 319.
【2】 Finke, P.E.; Mills, S.G.; Hale, J.J.; MacCoss, M. (Merck & Co., Inc.); Process of making chiral 2-aryl-1,4-butanediamine derivs.. WO 9407839 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	59283	N-(4-phenyl-4-piperidinyl)acetamide		C₁₃H₁₈N₂O	详情	详情
(XIV)	30414	2-(3,4-dichlorophenyl)acetic acid；2-(3,4-Dichlorophenyl)acetic acid	5807-30-7	C₈H₆Cl₂O₂	详情	详情
(XV)	58942			C₁₀H₁₀LiNO₂	详情	详情
(XVI)	62381	(4S)-4-benzyl-3-[2-(3,4-dichlorophenyl)acetyl]-1,3-oxazolidin-2-one		C₁₈H₁₅Cl₂NO₃	详情	详情
(XVII)	32112	3-iodo-1-propene;3-iodo-propen;allyl iodide	556-56-9	C₃H₅I	详情	详情
(XVIII)	62382	(4S)-4-benzyl-3-[(2S)-2-(3,4-dichlorophenyl)-4-pentenoyl]-1,3-oxazolidin-2-one		C₂₁H₁₉Cl₂NO₃	详情	详情
(XIX)	62383	(2S)-2-(3,4-dichlorophenyl)-4-pentenoic acid		C₁₁H₁₀Cl₂O₂	详情	详情
(XX)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(XXI)	50421	2-(3,4-dichlorophenyl)-4-pentenoic acid		C₁₁H₁₀Cl₂O₂	详情	详情
(XXII)	62384	(2S)-2-(3,4-dichlorophenyl)-N-methyl-4-pentenamide		C₁₂H₁₃Cl₂NO	详情	详情
(XXIII)	62385	(2S)-2-(3,4-dichlorophenyl)-N-methyl-4-penten-1-amine; N-[(2S)-2-(3,4-dichlorophenyl)-4-pentenyl]-N-methylamine		C₁₂H₁₅Cl₂N	详情	详情
(XXIV)	62386	N-[(2S)-2-(3,4-dichlorophenyl)-4-pentenyl]-N-methylbenzamide		C₁₉H₁₉Cl₂NO	详情	详情
(XXV)	62387	N-[(2S)-2-(3,4-dichlorophenyl)-4,5-dihydroxypentyl]-N-methylbenzamide		C₁₉H₂₁Cl₂NO₃	详情	详情
(XXVI)	26943	N-[(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methylbenzamide		C₁₈H₁₇Cl₂NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

Alternatively, 8-bromo-1-octene (IX) is converted into the corresponding Grignard reagent (X) which is further carboxylated by solid carbon dioxide in cold THF to produce acid (XI). Coupling of acid (XI) with the lithium derivative of (S)-4-benzyl-2-oxazolidinone (XII), via activation with pivalic anhydride, leads to the chiral N-acyl oxazolidinone (XIII). Stereoselective alpha-azidation of the potassium enolate of (XIII) with trizylazide forms the (S)-azide (XIV). Subsequent reduction of azide (XIV) employing SnCl2 leads to amine (XV), which is further protected as the N-Boc derivative (XVI) with Boc2O in the presence of NaHCO3. Then, hydrolysis of the chiral auxiliary of (XVI) by means of lithium hydroperoxide gives rise to the desired N-Boc aminoacid (VIII).

参考文献中间体

合成目标

【1】 Halmos, T.; Llinas-Brunet, M.; Faucher, A.-M.; Ghiro, E.; Goudreau, N.; Tsantrizos, Y.S.; Cameron, D.R. (Boehringer Ingelheim (Canada) Ltd.); Macrocyclic peptides active against the hepatitis C virus. EP 1169339; JP 2002542160; WO 0059929 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VIII)	58938	(2S)-2-[(tert-butoxycarbonyl)amino]-8-nonenoic acid	C₁₄H₂₅NO₄	详情	详情
(IX)	58939	8-Bromo-1-octene	C₈H₁₅Br	详情	详情
(X)	58940	bromo(7-octenyl)magnesium	C₈H₁₅BrMg	详情	详情
(XI)	58941	8-nonenoic acid	C₉H₁₆O₂	详情	详情
(XII)	58942		C₁₀H₁₀LiNO₂	详情	详情
(XIII)	58943	(4S)-4-benzyl-3-(8-nonenoyl)-1,3-oxazolidin-2-one	C₁₉H₂₅NO₃	详情	详情
(XIV)	58944	(4S)-3-[(2S)-2-azido-8-nonenoyl]-4-benzyl-1,3-oxazolidin-2-one	C₁₉H₂₄N₄O₃	详情	详情
(XV)	58945	(4S)-3-[(2S)-2-amino-8-nonenoyl]-4-benzyl-1,3-oxazolidin-2-one	C₁₉H₂₆N₂O₃	详情	详情
(XVI)	58946	tert-butyl (1S)-1-{[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-7-octenylcarbamate	C₂₄H₃₄N₂O₅	详情	详情

Extended Information