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【结 构 式】 
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【分子编号】55040 【品名】tert-butyl (1S)-1-formyl-2-[(3S)-2-oxopyrrolidinyl]ethylcarbamate 【CA登记号】 |
【 分 子 式 】C12H20N2O4 【 分 子 量 】256.30188 【元素组成】C 56.24% H 7.87% N 10.93% O 24.97% |
合成路线1
该中间体在本合成路线中的序号：(VII)The alkylation of dimethyl L-glutamate (I) with 2-bromoacetonitrile (II) by means of LiHMDS in THF gives stereoselectively the cyanomethyl derivative (III), which is reduced with H2 over PtO2 in methanol/CHCl3 to yield the corresponding 2-aminoethyl derivative (IV). The cyclization of (IV) by means of Na2CO3 in the same solvent affords the pyrrolidinone (V), whose ester group is reduced with NaBH4 in methanol/THF to provide the propanol derivative (VI). The oxidation of (VI) with SO3/pyridine and DIEA in DMSO/dichloromethane gives the aldehyde (VII), which is finally condensed with ethyl 2-bromoacetate (VIII) by means of Et3P in dichloromethane to yield the chiral 4-(tert-butoxycarbonyl)-5-(2-oxopyrrolidin-3-yl)-2-pentanoic acid ethyl ester (IX), the desired target key intermediate.
| 【1】 Tian, Q.; et al.; An efficient synthesis of a key intermediate for the preparation of the rhinovirus protease inhibitor AG7088 via asymmetric dianionic cyanomethylation of N-Boc-L-(+)-glutamic acid dimethyl ester. Tetrahedron Lett 2001, 42, 39, 6807. |
| 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) | 55035 | dimethyl (2S)-2-[(tert-butoxycarbonyl)amino]pentanedioate | C12H21NO6 | 详情 | 详情 | |
| (II) | 31883 | 2-bromoacetonitrile | 590-17-0 | C2H2BrN | 详情 | 详情 |
| (III) | 55036 | dimethyl (2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-(cyanomethyl)pentanedioate | C14H22N2O6 | 详情 | 详情 | |
| (IV) | 55037 | dimethyl (2S,4S)-2-(2-aminoethyl)-4-[(tert-butoxycarbonyl)amino]pentanedioate | C14H26N2O6 | 详情 | 详情 | |
| (V) | 55038 | methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-[(3S)-2-oxopyrrolidinyl]propanoate | C13H22N2O5 | 详情 | 详情 | |
| (VI) | 55039 | tert-butyl (1S)-2-hydroxy-1-{[(3S)-2-oxopyrrolidinyl]methyl}ethylcarbamate | C12H22N2O4 | 详情 | 详情 | |
| (VII) | 55040 | tert-butyl (1S)-1-formyl-2-[(3S)-2-oxopyrrolidinyl]ethylcarbamate | C12H20N2O4 | 详情 | 详情 | |
| (VIII) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (IX) | 55041 | ethyl (E,4S)-4-[(tert-butoxycarbonyl)amino]-5-[(3S)-2-oxopyrrolidinyl]-2-pentenoate | C16H26N2O5 | 详情 | 详情 |