(5R)-3-[4-(benzyloxy)phenyl]-5-(methoxymethyl)-1,3-oxazolidin-2-one -Drug Synthesis Database

【结构式】

【分子编号】28690

【品名】(5R)-3-[4-(benzyloxy)phenyl]-5-(methoxymethyl)-1,3-oxazolidin-2-one

【CA登记号】

【分子式】C₁₈H₁₉NO₄

【分子量】313.3532

【元素组成】C 68.99% H 6.11% N 4.47% O 20.42%

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：(IV)

The condensation of p-benzyloxyaniline (I) with 1-chloro-2-hydroxy-3-methoxypropane (II) in ethanol, followed by cyclization ot the resulting amino alcohol (III) with ethyl carbonate (A) in toluene in the presence of CH3ONa and debenzylation affords a phenolic 2-oxazolidinone (V), which is alkylated with m-cyanobenzyl bromide (VI) to give cimoxatone.

参考文献中间体

合成目标

【1】 Ancher, J.F.; Bourgery, G.; Dostert, P.; Douzon, C.; Guerret, P.; Lacour, A.; Laglois, M.; Nouvelles oxazolidinones, oxazolidinethiones et pyrrilidinones, leur procédé de préparation et leur application en thérapeutique. FR 2428032; JP 55051064; JP 56167666 .
【2】 Ancher, J.F.; Cimoxatone. Drugs Fut 1984, 9, 6, 412.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	17470	diethyl carbonate; diethylcarbonate	105-58-8	C₅H₁₀O₃	详情	详情
(I)	22460	4-(benzyloxy)aniline; 4-(benzyloxy)phenylamine		C₁₃H₁₃NO	详情	详情
(II)	34214	1-chloro-3-methoxy-2-propanol	4151-97-7	C₄H₉ClO₂	详情	详情
(III)	34215	1-[4-(benzyloxy)anilino]-3-methoxy-2-propanol		C₁₇H₂₁NO₃	详情	详情
(IV)	28690	(5R)-3-[4-(benzyloxy)phenyl]-5-(methoxymethyl)-1,3-oxazolidin-2-one		C₁₈H₁₉NO₄	详情	详情
(V)	28682	(5R)-3-(4-hydroxyphenyl)-5-(methoxymethyl)-1,3-oxazolidin-2-one		C₁₁H₁₃NO₄	详情	详情
(VI)	13244	alpha-Bromo-m-tolunitrile; 3-(Bromomethyl)benzonitrile	28188-41-2	C₈H₆BrN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

2) Synthesis of Oxazolidinone (II): 2a) The reaction of 4-benzyloxyaniline (IX) with 1,4-dioxaspiro[4.5]decan-2(S)-ylmethyl methanesulfonate (X) by means of TEA at 140 C gives 3-(4-benzyloxyphenylamino)propane-1,2(R)-diol (XI), which is cyclized with diethyl carbonate and sodium methoxide in refluxing toluene, yielding 3-(4-benzyloxyphenyl)-5(R)-(hydroxymethyl)oxazolidin-2-one (XII). The methylation of (XII) with dimethyl sulfate, NaOH and tetrabutylammonium bisulfate in hot toluene/water affords the corresponding methoxymethyl derivative (XIII). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C in ethanol/dichloromethane to give oxazolidinone (II). 2b) The methylation of 4(S)-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane (XIV) with dimethyl sulfate and NaOH gives 4(S)-(methoxymethyl)-2,2-dimethyl-1,3-dioxolane (XV), which is hydrolyzed with hot aqueous HCl to 3-methoxypropane-1,2(R)-diol (XVI). The cyclization of (XVI) with diethyl carbonate by means of NaH affords 4(S)-(methoxymethyl)-1,3-dioxolan-2-one (XVII) (2, 5). The condensation of (XVII) with N-(4-benzyloxyphenyl)carbamic acid methyl ester (XVIII) (obtained by reaction of 4-benzyloxyaniline (IX) with methyl chloroformate) by means of K2CO3 at 160 C provides the protected oxazolidinone (XIII), which is finally debenzylated as before to give oxazolidinone (II).

参考文献中间体

合成目标

【1】 Castaner, J.; Sorbera, L.A.; Rabasseda, X.; Befloxatone. Drugs Fut 1999, 24, 10, 1057.
【2】 Koenig, J.-J.; Schoofs, A.; Jarreau, F.-X.; Rovei, V. (Laboratoires Delalande); 3-Aryl oxazolidinones, process for their preparation and their therapeutical use. EP 0424243; EP 0424244; EP 0428421; JP 1992502333; JP 1992502334; JP 1992502335; US 5036090; US 5036091; US 5171747; US 5196543; WO 9105775 .
【3】 Jarreau, F.-X.; Koenig, J.-J.; Rovei, V. (Laboratoires Delalande); 3-Aryl-oxazolidinone derivs., process for their preparation and their use in therapeutics. EP 0511031; FR 2675504; JP 1993112542; US 5264443 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	28682	(5R)-3-(4-hydroxyphenyl)-5-(methoxymethyl)-1,3-oxazolidin-2-one		C₁₁H₁₃NO₄	详情	详情
(IX)	22460	4-(benzyloxy)aniline; 4-(benzyloxy)phenylamine		C₁₃H₁₃NO	详情	详情
(X)	28688	(2R)-1,4-dioxaspiro[4.5]dec-2-ylmethyl methanesulfonate		C₁₀H₁₈O₅S	详情	详情
(XI)	28689	(2R)-3-[4-(benzyloxy)anilino]-1,2-propanediol		C₁₆H₁₉NO₃	详情	详情
(XII)	28695	(5R)-3-[4-(benzyloxy)phenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one		C₁₇H₁₇NO₄	详情	详情
(XIII)	28690	(5R)-3-[4-(benzyloxy)phenyl]-5-(methoxymethyl)-1,3-oxazolidin-2-one		C₁₈H₁₉NO₄	详情	详情
(XIV)	12709	[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]methanol	22323-82-6	C₆H₁₂O₃	详情	详情
(XV)	28691	(4S)-4-(methoxymethyl)-2,2-dimethyl-1,3-dioxolane		C₇H₁₄O₃	详情	详情
(XVI)	28692	(2R)-3-methoxy-1,2-propanediol		C₄H₁₀O₃	详情	详情
(XVII)	28693	(4S)-4-(methoxymethyl)-1,3-dioxolan-2-one		C₅H₈O₄	详情	详情
(XVIII)	28694	methyl 4-(benzyloxy)phenylcarbamate		C₁₅H₁₅NO₃	详情	详情

Extended Information