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【结 构 式】 
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【分子编号】50641 【品名】1,3-Dioxaindane; 1,3-Benzodioxole; methylenedioxybenzene; 1,2-methylenedioxybenzene; catechol methylene ether 【CA登记号】274-09-9 |
【 分 子 式 】C7H6O2 【 分 子 量 】122.12344 【元素组成】C 68.85% H 4.95% O 26.2% |
合成路线1
该中间体在本合成路线中的序号：(XXXVII)The preferred synthetic route began with the Friedel-Crafts acylation of benzodioxol (XXXVII) by means of butyric anhydride and BF3. The resultant butyrophenone (XIII) was then condensed with (R)-1-phenylethylamine (XXXVII), using TiCl4 as the dehydrating reagent, to afford the E-imine (XXXIX) as the major isomer. Catalytic hydrogenation of imine (XXXIX) in the presence of Raney-Ni furnished the desired amine (XL). The chiral auxiliary was then removed by hydrogenolysis over Pd/C to yield amine (XVII).
| 【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. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 53629 | 1-(1,3-benzodioxol-5-yl)-1-butanone | 63740-97-6 | C11H12O3 | 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 |
| (XXVIII) | 10039 | (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine | 3886-69-9 | C8H11N | 详情 | 详情 |
| (XXXVII) | 50641 | 1,3-Dioxaindane; 1,3-Benzodioxole; methylenedioxybenzene; 1,2-methylenedioxybenzene; catechol methylene ether | 274-09-9 | C7H6O2 | 详情 | 详情 |
| (XXXIX) | 53649 | (1R)-N-[(E)-1-(1,3-benzodioxol-5-yl)butylidene]-1-phenyl-1-ethanamine; N-[(E)-1-(1,3-benzodioxol-5-yl)butylidene]-N-[(1R)-1-phenylethyl]amine | n/a | C19H21NO2 | 详情 | 详情 |
| (XL) | 53650 | N-[(1R)-1-(1,3-benzodioxol-5-yl)butyl]-N-[(1R)-1-phenylethyl]amine; (1R)-1-(1,3-benzodioxol-5-yl)-N-[(1R)-1-phenylethyl]-1-butanamine | n/a | C19H23NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Lithiation of 5-bromo-1,3-benzodioxole (I), followed by reaction with elemental sulfur gave disulfide (II), which was reduced to thiol (III) by using LiAlH4. In an alternative procedure, thiol (III) was prepared by chlorosulfonation of benzodioxole (IV) and then reduction of the resulting sulfonyl chloride (V) with LiAlH4. Condensation of thiol (III) with p-fluoroacetophenone (VI) provided the diaryl sulfide (VII). Asymmetric reduction of the keto group of (VII) employing borane-dimethyl sulfide complex in the presence of the chiral oxazaborole auxiliary (VIII) yielded the (R)-alcohol (IX), which was converted to mesylate (XI) by oxidation with MCPBA to sulfone (X), a treatment with methanesulfonyl chloride and triethylamine. Alkylation of benzyl (R)-3-methylpiperazine-1-carboxylate (XII) with the chiral mesylate (XI) gave adduct (XIII). The benzyloxycarbonyl protecting group of (XIII) was then removed by acid hydrolysis, yielding piperazine (XIV).
| 【1】 Muscarinic antagonists. WO 9805292 . |
| 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) | 10124 | 5-Bromo-1,3-benzodioxole; 4-Bromo-1,2-(methylenedioxy)benzene | 2635-13-4 | C7H5BrO2 | 详情 | 详情 |
| (II) | 50640 | 5-(1,3-benzodioxol-5-yldisulfanyl)-1,3-benzodioxole; di(1,3-benzodioxol-5-yl) disulfide | C14H10O4S2 | 详情 | 详情 | |
| (III) | 28620 | 1,3-benzodioxole-5-thiol | C7H6O2S | 详情 | 详情 | |
| (IV) | 50641 | 1,3-Dioxaindane; 1,3-Benzodioxole; methylenedioxybenzene; 1,2-methylenedioxybenzene; catechol methylene ether | 274-09-9 | C7H6O2 | 详情 | 详情 |
| (V) | 50642 | 1,3-benzodioxole-5-sulfonyl chloride | C7H5ClO4S | 详情 | 详情 | |
| (VI) | 37684 | 1-(4-fluorophenyl)-1-ethanone | 403-42-9 | C8H7FO | 详情 | 详情 |
| (VII) | 50643 | 1-[4-(1,3-benzodioxol-5-ylsulfanyl)phenyl]-1-ethanone | C15H12O3S | 详情 | 详情 | |
| (VIII) | 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 |
| (IX) | 50644 | (1R)-1-[4-(1,3-benzodioxol-5-ylsulfanyl)phenyl]-1-ethanol | C15H14O3S | 详情 | 详情 | |
| (X) | 50645 | (1R)-1-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]-1-ethanol | C15H14O5S | 详情 | 详情 | |
| (XI) | 50646 | (1R)-1-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]ethyl methanesulfonate | C16H16O7S2 | 详情 | 详情 | |
| (XII) | 50647 | benzyl (3R)-3-methyl-1-piperazinecarboxylate | C13H18N2O2 | 详情 | 详情 | |
| (XIII) | 50648 | benzyl (3R)-4-[(1S)-1-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]ethyl]-3-methyl-1-piperazinecarboxylate | C28H30N2O6S | 详情 | 详情 | |
| (XIV) | 50649 | (2R)-1-[(1S)-1-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]ethyl]-2-methylpiperazine; 1,3-benzodioxol-5-yl 4-[(1S)-1-[(2R)-2-methylpiperazinyl]ethyl]phenyl sulfone | C20H24N2O4S | 详情 | 详情 |