【结 构 式】 |
【分子编号】28693 【品名】(4S)-4-(methoxymethyl)-1,3-dioxolan-2-one 【CA登记号】 |
【 分 子 式 】C5H8O4 【 分 子 量 】132.11612 【元素组成】C 45.46% H 6.1% O 48.44% |
合成路线1
该中间体在本合成路线中的序号:(XVII)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).
【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 |