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【结 构 式】 
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【分子编号】53634 【品名】1,1-dimethylpropanoic 4-[(2,2-dimethylpropanoyl)oxy]-1-benzenecarboxylic anhydride 【CA登记号】n/a |
【 分 子 式 】C17H22O5 【 分 子 量 】306.35868 【元素组成】C 66.65% H 7.24% O 26.11% |
合成路线1
该中间体在本合成路线中的序号：(XX)In a further procedure, 4-hydroxybenzoic acid (XIX) was converted to amide (XXII) via formation of the mixed anhydride-ester (XX) with pivaloyl chloride, followed by coupling with N-methylpiperazine (III) and alcoholysis of the resultant amide-ester (XXI) or, alternatively, by direct coupling of acid (XIX) with piperazine (III) in the presence of DCC. The propionate group of azetidinone (IV) was then displaced by the 4-hydroxybenzamide (XXII) to give the racemic adduct (XXIII). Resolution of (XXIII) by means of (-)-diisopropylidene ketogulonic acid (DAG) provided the desired enantiomer (IX), which was finally converted into the title compound by condensation with isocyanate (XVIII) in the presence of DBU in acetonitrile.
| 【1】 Storace, L.; et al.; An efficient large-scale process for the human leukocyte elastase inhibitor, DMP 777. Org Process Res Dev 2002, 6, 1, 54. |
| 【2】 Li, H.-Y.; Fortunak, J.M.; Storace, L.; Sheeran, P.J.; Anzalone, L. (DuPont Pharmaceuticals Co.); An efficient process for the preparation of a human leukocyte elastase inhibitor. WO 0012474 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (IV) | 53621 | 3,3-diethyl-4-oxo-2-azetidinyl propionate | n/a | C10H17NO3 | 详情 | 详情 |
| (IX) | 53626 | (4S)-3,3-diethyl-4-{4-[(4-methyl-1-piperazinyl)carbonyl]phenoxy}-2-azetidinone | n/a | C19H27N3O3 | 详情 | 详情 |
| (XVIII) | 53632 | 5-[(1R)-1-isocyanatobutyl]-1,3-benzodioxole; (1R)-1-(1,3-benzodioxol-5-yl)butyl isocyanate | n/a | C12H13NO3 | 详情 | 详情 |
| (XIX) | 28205 | 4-hydroxybenzoic acid | 99-96-7 | C7H6O3 | 详情 | 详情 |
| (XX) | 53634 | 1,1-dimethylpropanoic 4-[(2,2-dimethylpropanoyl)oxy]-1-benzenecarboxylic anhydride | n/a | C17H22O5 | 详情 | 详情 |
| (XXI) | 53635 | 4-[(4-methyl-1-piperazinyl)carbonyl]phenyl pivalate | n/a | C17H24N2O3 | 详情 | 详情 |
| (XXII) | 53633 | (4-hydroxyphenyl)(4-methyl-1-piperazinyl)methanone | n/a | C12H16N2O2 | 详情 | 详情 |
| (XXIII) | 53636 | 3,3-diethyl-4-{4-[(4-methyl-1-piperazinyl)carbonyl]phenoxy}-2-azetidinone | n/a | C19H27N3O3 | 详情 | 详情 |