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【结 构 式】 
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【分子编号】47791 【品名】methyl 2-(dichloromethyl)-4,5-dihydro-1,3-oxazole-4-carboxylate 【CA登记号】 |
【 分 子 式 】C6H7Cl2NO3 【 分 子 量 】212.03192 【元素组成】C 33.99% H 3.33% Cl 33.44% N 6.61% O 22.64% |
合成路线1
该中间体在本合成路线中的序号：(IV)Synthesis of oxazole intermediate (IX): The reaction of 2,2-dichloroacetonitrile (I) with sodium methoxide in methanol gives methyl 2,2-dichloroethanimidoate (II), which is cyclized with DL-serine methyl ester (III) in methanol to yield oxazoline (IV). The reaction of (IV) with sodium methoxide in methanol affords 2-(chloromethyl)-4-methoxy-4,5-dihydrooxazole-4-carboxylic acid methyl ester (V), which is treated with Ts-OH in refluxing toluene to provide the chloromethyloxazole (VI). The reaction of (VI) with pyrrolidine (VII) in toluene gives the 2-(1-pyrrolidinylmethyl)oxazole-4-carboxylic acid methyl ester (VIII), which is hydrolyzed with K2CO3 to yield the target oxazole (IX). Alternatively, the reaction of 2-(bromomethyl)oxazole-4-carboxylic acid ethyl ester (X) with pyrrolidine (VII) gives the precursor (XI), which is hydrolyzed with K2CO3 as before to afford the target oxazole intermediate (IX).
| 【1】 Hermitage, S.A.; et al.; An efficient, practical approach to the synthesis of 2,4-disubstituted thiazoles and oxazoles: Application to the synthesis of GW475151. Org Process Res Dev 2001, 5, 1, 37. |
| 【2】 Johnson, M.R.; Shah, P.; MacDonald, S.J.F.; Harrison, L.A.; Finch, H.; Smith, R.A.; Inglis, G.G.A.; Clarke, G.D.E.; Dowle, M.D. (Glaxo Group Ltd.); Pyrrolopyrrolone derivs. as inhibitors of neutrophil elastase. WO 9912933 . |
| 【3】 Hermitage, S.A.; Cardwell, K.S. (Glaxo Group Ltd.); Process for preparing oxazole derivs.. WO 0053589 . |
| 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) | 47789 | 2,2-dichloroacetonitrile; Dichloroacetonitrile | 3018-12-0 | C2HCl2N | 详情 | 详情 |
| (II) | 47790 | methyl 2,2-dichloroethanimidoate | C3H5Cl2NO | 详情 | 详情 | |
| (III) | 14224 | Serine, methyl ester; methyl 2-amino-3-hydroxypropanoate | 2104-89-4 | C4H9NO3 | 详情 | 详情 |
| (IV) | 47791 | methyl 2-(dichloromethyl)-4,5-dihydro-1,3-oxazole-4-carboxylate | C6H7Cl2NO3 | 详情 | 详情 | |
| (V) | 47792 | methyl 2-(chloromethyl)-4-methoxy-4,5-dihydro-1,3-oxazole-4-carboxylate | C7H10ClNO4 | 详情 | 详情 | |
| (VI) | 47793 | methyl 2-(chloromethyl)-1,3-oxazole-4-carboxylate | C6H6ClNO3 | 详情 | 详情 | |
| (VII) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (VIII) | 47794 | methyl 2-(1-pyrrolidinylmethyl)-1,3-oxazole-4-carboxylate | C10H14N2O3 | 详情 | 详情 | |
| (IX) | 47795 | potassium 2-(1-pyrrolidinylmethyl)-1,3-oxazole-4-carboxylate | C9H11KN2O3 | 详情 | 详情 | |
| (X) | 47796 | ethyl 2-(bromomethyl)-1,3-oxazole-4-carboxylate | C7H8BrNO3 | 详情 | 详情 | |
| (XI) | 47797 | ethyl 2-(1-pyrrolidinylmethyl)-1,3-oxazole-4-carboxylate | C11H16N2O3 | 详情 | 详情 |