|
【结 构 式】 
|
【分子编号】53627 【品名】trifluoro-N-((1R,2R)-2-{[(trifluoromethyl)sulfonyl]amino}cyclohexyl)methanesulfonamide 【CA登记号】n/a |
【 分 子 式 】C8H12F6N2O4S2 【 分 子 量 】378.3167792 【元素组成】C 25.4% H 3.2% F 30.13% N 7.4% O 16.92% S 16.95% |
合成路线1
该中间体在本合成路线中的序号：(XI)The required (S)-alpha-propylpiperonyl alcohol (XV) was prepared by two alternative routes. Asymmetric addition of di-n-propyl zinc to piperonal (X) in the presence of titanium isopropoxide and the chiral bis-triflamide (XI) yielded the (S)-alcohol (XV) in high enantiomeric excess. Alternatively, ketone (XIII) was reduced with the oxazaborolidine-borane complex (XIV) to give (XV). Treatment of the (S)-alcohol (XV) with DPPA in the presence of DBU produced the (R)-azide (XVI). This was then reduced with LiAlH4 to yield amine (XVII) with some loss of optical purity. Optical enrichment was achieved by crystallization as the D-pyroglutamic acid salt. The (R)-amine (XVII) was converted to isocyanate (XVIII) by treatment with phosgene. Finally, coupling between isocyanate (XVIII) and azetidinone (IX) in the presence of DBU in acetonitrile led to the title compound.
| 【1】 Cvetovich, R.J.; et al.; An asymmetric synthesis of L-694,458, a human leukocyte elastase inhibitor, via novel enzyme resolution of beta-lactam esters. J Org Chem 1996, 61, 19, 6575. |
| 【2】 Amato, J.S.; Cvetovich, R.; Hartner, F.W. (Merck & Co., Inc.); Process for preparing substd. azetidinones. WO 9716448 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 53626 | (4S)-3,3-diethyl-4-{4-[(4-methyl-1-piperazinyl)carbonyl]phenoxy}-2-azetidinone | n/a | C19H27N3O3 | 详情 | 详情 |
| (X) | 10127 | 1,3-Benzodioxole-5-carbaldehyde; Heliotropine | 120-57-0 | C8H6O3 | 详情 | 详情 |
| (XI) | 53627 | trifluoro-N-((1R,2R)-2-{[(trifluoromethyl)sulfonyl]amino}cyclohexyl)methanesulfonamide | n/a | C8H12F6N2O4S2 | 详情 | 详情 |
| (XIII) | 53629 | 1-(1,3-benzodioxol-5-yl)-1-butanone | 63740-97-6 | C11H12O3 | 详情 | 详情 |
| (XIV) | 20631 | (R)-Methyl oxazaborolidine; (3aR)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-83-0 | C18H20BNO | 详情 | 详情 |
| (XV) | 53628 | (1S)-1-(1,3-benzodioxol-5-yl)-1-butanol | n/a | C11H14O3 | 详情 | 详情 |
| (XVI) | 53630 | (1R)-1-(1,3-benzodioxol-5-yl)butyl azide; 5-[(1R)-1-azidobutyl]-1,3-benzodioxole | n/a | C11H13N3O2 | 详情 | 详情 |
| (XVII) | 53631 | (1R)-1-(1,3-benzodioxol-5-yl)-1-butanamine; (1R)-1-(1,3-benzodioxol-5-yl)butylamine | n/a | C11H15NO2 | 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 |