【结 构 式】 |
【分子编号】36795 【品名】N-[4-(2-chloroacetyl)phenyl]methanesulfonamide 【CA登记号】64488-52-4 |
【 分 子 式 】C9H10ClNO3S 【 分 子 量 】247.70204 【元素组成】C 43.64% H 4.07% Cl 14.31% N 5.65% O 19.38% S 12.95% |
合成路线1
该中间体在本合成路线中的序号:(I)A chiral synthesis of d-sotalol has been reported starting from the commercially available 4'-(chloroacetyl)methanesulfonanilide (I). Enantioselective ketone reduction employing borane-tetrahydrofuran complex and (S)-2-methyloxazaborolidine (II) in tert-butyl methyl ether aforded the (S)-alcohol (III) with 96% e.e. Protection of the hydroxyl group as the triethylsilyl ether (IV) avoided formation of the undesired epoxide. Nucleophilic displacement of the chlorine of (IV) with isopropylamine to yield (V) was effected at 130 C in a pressurized steel bomb. Then, desilylation of (V) with tetrabutylammonium fluoride, followed by conversion to the hydrochloride salt furnished the title compound. In an improved procedure, chloride (III) was converted to the corresponding iodide (VI) by Finkelstein reaction with NaI in boiling acetone, followed by silylation with triethylsilyl chloride and imidazole to give (VII). Displacement of the iodine of (VII) to produce (V) was then feasible with refluxing isopropylamine at atmospheric pressure.
【1】 Brodfuehrer, P.R.; et al.; Asymmetric synthesis of the antiarrhythmia agent d-sotalol. Org Process Res Dev 1997, 1, 2, 176. |
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) | 36795 | N-[4-(2-chloroacetyl)phenyl]methanesulfonamide | 64488-52-4 | C9H10ClNO3S | 详情 | 详情 |
(II) | 28292 | (S)-Methyl oxazaborolidine; (3aS)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-81-8 | C18H20BNO | 详情 | 详情 |
(III) | 36796 | N-[4-[(1S)-2-chloro-1-hydroxyethyl]phenyl]methanesulfonamide | C9H12ClNO3S | 详情 | 详情 | |
(IV) | 36797 | N-(4-[(1S)-2-chloro-1-[(triethylsilyl)oxy]ethyl]phenyl)methanesulfonamide | C15H26ClNO3SSi | 详情 | 详情 | |
(V) | 36798 | N-(4-[(1S)-2-(isopropylamino)-1-[(triethylsilyl)oxy]ethyl]phenyl)methanesulfonamide | C18H34N2O3SSi | 详情 | 详情 | |
(VI) | 36799 | N-[4-[(1S)-1-hydroxy-2-iodoethyl]phenyl]methanesulfonamide | C9H12INO3S | 详情 | 详情 | |
(VII) | 36800 | ----N-(4-[(1S)-2-iodo-1-[(triethylsilyl)oxy]ethyl]phenyl)methanesulfonamide | C15H26INO3SSi | 详情 | 详情 |