2-[(4-Methoxybenzyl)oxy]acetyl chloride -Drug Synthesis Database

【结构式】

【分子编号】10610

【品名】2-[(4-Methoxybenzyl)oxy]acetyl chloride

【CA登记号】

【分子式】C₁₀H₁₁ClO₃

【分子量】214.64824

【元素组成】C 55.96% H 5.17% Cl 16.52% O 22.36%

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)

A new synthesis of paclitaxel has been described: The condensation of Oppolzer's L-(+)-2,10-camphorsultam (I) with 2-(4-methoxybenzyloxy)acetyl chloride (II) by means of NaH gives the corresponding substituted sultam (III), which is condensed with N-benzoylbenzaldehydeimine (IV) by means of lithium bis(trimethylsilyl)amide, yielding the protected side-chain (V) of paclitaxel. The reaction of (V) with DDQ affords oxazolidine (VI), which is hydrolyzed with LiOH/H2O2 to the free oxazolidine-carboxylic acid (VII). The esterification of (VII) with baccatin III (VIII) by means of dicyclohexylcarbodiimide (DCC) affords the protected paclitaxel derivative (IX), which is finally treated with HCl in ethanol.

参考文献中间体

合成目标

【1】 Kanazawa, A.M.; Greene, A.E.; Denis, J.-N.; Direct, stereoselective synthesis of the protected paclitaxel (Taxol) side chain and high-yield transformation to paclitaxel. J Chem Soc Chem Commun 1994, 2591.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	10609	(1R,5S,7S)-10,10-Dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione	C₁₀H₁₇NO₂S	详情	详情
(II)	10610	2-[(4-Methoxybenzyl)oxy]acetyl chloride	C₁₀H₁₁ClO₃	详情	详情
(III)	10611	(1R,5S,7S)-4-[2-[(4-Methoxybenzyl)oxy]acetyl]-10,10-dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione	C₂₀H₂₇NO₅S	详情	详情
(IV)	10612	N-[(Z)-Benzylidene]benzamide	C₁₄H₁₁NO	详情	详情
(V)	10613	N-[(1S,2R)-3-[(1R,5S,7S)-10,10-Dimethyl-3,3-dioxo-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]dec-4-yl]-2-[(4-methoxybenzyl)oxy]-3-oxo-1-phenylpropyl]benzamide	C₃₄H₃₈N₂O₆S	详情	详情
(VI)	10614	(1R,5S,7S)-4-[[(4S,5R)-3-Benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidin-5-yl]carbonyl]-10,10-dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione	C₃₄H₃₆N₂O₆S	详情	详情
(VII)	10615	(4S,5R)-3-Benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid	C₂₄H₂₁NO₅	详情	详情
(VIII)	10473	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate	C₃₇H₅₂O₁₁Si	详情	详情
(IX)	57903	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-15-yl (2R,4S,5R)-3-benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate	C₆₁H₇₁NO₁₅Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Acetylation of substituted aniline (I) with acetic anhydride in refluxing acetic acid affords acetanilide (II), which is then nitrated with HNO3:H2SO4 to provide 2-nitro derivative (III). Hydrolysis of (III) in concentrated H2SO4 gives substituted 2-nitroaniline (IV), which is then subjected to diazotization with NaNO2 and HCl in H2O and then treated with NaN3 and sodium acetate in H2O to furnish 2-nitrophenyl azide derivative (V). Cyclocondensation of azide (V) in refluxing toluene yields benzofuroxane (VI), which in turn is subjected to Beirut reaction with malonitrile (VII) in DMF in the presence of Et3N to yield 3-amino-2-quinoxalinecarbonitrile 1,4-di-N-oxide (VIII). The amino group of (VIII) is replaced by chlorine by using tert-butyl nitrite in acetonitrile in the presence of copper (II) chloride to give compound (IX). Finally, the target compound is obtained by reaction of (IX) with 1-(4-nitro-phenyl)piperazine (X) in dichloromethane or CHCl3 in the presence of Na2CO3 or K2CO3.

参考文献中间体

合成目标

【1】 Jaso, A.; Montoya, M.E.; Monge, A.; Zarranz, B.; Ortega, M.A.; Tirapu, I.; Aldana, I.; Antimycobacterial activity of new quinoxaline-2-carbonitrile and quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives. Pharmazie 2001, 56, 3, 205.
【2】 Monge, A.; et al.; Hypoxia-selective agents derived from quinoxaline 1, 4-di-N-oxides. J Med Chem 1995, 38, 10, 1786.
【3】 Ortega, M.A.; et al.; New quinoxalinecarbonitrile 1,4-di-N-oxide derivatives as hypoxic-cytotoxic agents. Eur J Med Chem 2000, 35, 1, 21.

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)	33707	3,4-dimethylphenylamine; 3,4-dimethylaniline	95-64-7	C₈H₁₁N	详情	详情
(II)	50101	N-Acetyl-3,4-xylidine; 3,4-Dimethylacetanilide	2198-54-1	C₁₀H₁₃NO	详情	详情
(III)	50102	4',5'-Dimethyl-2'-nitroacetanilide		C₁₀H₁₂N₂O₃	详情	详情
(IV)	50103	2-Nitro-4,5-dimethylaniline; 6-Nitro-3,4-xylidine; 4,5-Dimethyl-2-nitroaniline	6972-71-0	C₈H₁₀N₂O₂	详情	详情
(V)	50104	1-azido-4,5-dimethyl-2-nitrobenzene		C₈H₈N₄O₂	详情	详情
(VI)	50105	5,6-dimethyl-2,1,3-benzoxadiazol-1-ium-1-olate		C₈H₈N₂O₂	详情	详情
(VII)	10610	2-[(4-Methoxybenzyl)oxy]acetyl chloride		C₁₀H₁₁ClO₃	详情	详情
(VIII)	50106	2-amino-3-cyano-6,7-dimethyl-1,4-quinoxalinediiumdiolate		C₁₁H₁₀N₄O₂	详情	详情
(IX)	50107	2-chloro-3-cyano-6,7-dimethyl-1,4-quinoxalinediiumdiolate		C₁₁H₈ClN₃O₂	详情	详情
(X)	20299	1-(4-nitrophenyl)piperazine	6269-89-2	C₁₀H₁₃N₃O₂	详情	详情

Extended Information