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【结 构 式】 
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【分子编号】56471 【品名】N-(3,5-dimethylphenyl)-N-[(2S,3R)-3-hydroxy-4,7,7-trimethylbicyclo[2.2.1]hept-2-yl]benzenesulfonamide 【CA登记号】 |
【 分 子 式 】C24H31NO3S 【 分 子 量 】413.58108 【元素组成】C 69.7% H 7.56% N 3.39% O 11.61% S 7.75% |
合成路线1
该中间体在本合成路线中的序号：(IV)The condensation of 1-(tert-butoxycarbonyl)piperidin-2-one (I) with methyl chloroformate (II) by means of LHMDS in THF gives 1-(tert-butoxycarbonyl)-2-oxopiperidine-3-carboxylic acid methyl ester (III), which is transesterified with the chiral auxiliary (IV) by means of DMAP in refluxing toluene to yield the shielded ester (V). The reaction of (V) with phenylselanyl chloride and NaH in THF/HMPA affords the selenide (VI), which is treated with H2O2 to produce an oxidative deselenation to afford the unsaturated ester (VII). The addition of lithium di(4-fluorophenyl)cuprate (VIII) to the asymmetric olefinic amidoester (VII) leads to the addition product (IX). Finally, the reductive cleavage of the chiral auxiliary by reduction with LiAlH4 in refluxing THF produces the simultaneous reduction of the tert-butoxycarbonyl group to afford the target intermediate, the (3S,4R)-4-(4-fluorophenyl-3-(hydroxymethyl)-1-methylpiperidine (X) (see scheme no. 10786004a, intermediate (V)).
| 【1】 Cossy, J.; et al.; A short formal synthesis of paroxetine. Diastereoselective cuprate addition to a chiral racemic olefinic amido ester. Tetrahedron Lett 2001, 42, 44, 7805. |
| 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) | 56469 | tert-butyl 2-oxo-1-piperidinecarboxylate | C10H17NO3 | 详情 | 详情 | |
| (II) | 16993 | methyl chlorocarbonate;Carbonochloridic acid methyl ester；[(chlorocarbonyl)oxy]methane；methyl chloroformate | 79-22-1 | C2H3ClO2 | 详情 | 详情 |
| (III) | 56470 | 1-(tert-butyl) 3-methyl 2-oxo-1,3-piperidinedicarboxylate | C12H19NO5 | 详情 | 详情 | |
| (IV) | 56471 | N-(3,5-dimethylphenyl)-N-[(2S,3R)-3-hydroxy-4,7,7-trimethylbicyclo[2.2.1]hept-2-yl]benzenesulfonamide | C24H31NO3S | 详情 | 详情 | |
| (V) | 56472 | 1-(tert-butyl) 3-{(2R,3S)-3-[3,5-dimethyl(phenylsulfonyl)anilino]-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl} 2-oxo-1,3-piperidinedicarboxylate | C35H46N2O7S | 详情 | 详情 | |
| (VI) | 56473 | 1-(tert-butyl) 3-{(2R,3S)-3-[3,5-dimethyl(phenylsulfonyl)anilino]-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl} 2-oxo-3-(phenylselanyl)-1,3-piperidinedicarboxylate | C41H50N2O7SSe | 详情 | 详情 | |
| (VII) | 56474 | 1-(tert-butyl) 3-{(2R,3S)-3-[3,5-dimethyl(phenylsulfonyl)anilino]-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl} 2-oxo-5,6-dihydro-1,3(2H)-pyridinedicarboxylate | C35H44N2O7S | 详情 | 详情 | |
| (VIII) | 56475 | C27H25CuF4Li | 详情 | 详情 | ||
| (IX) | 56476 | 1-(tert-butyl) 3-{(2R,3S)-3-[3,5-dimethyl(phenylsulfonyl)anilino]-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl} (3S,4R)-4-(4-fluorophenyl)-2-oxo-1,3-piperidinedicarboxylate | C41H49FN2O7S | 详情 | 详情 | |
| (X) | 56477 | (3R,4R)-4-(4-fluorophenyl)-3-(hydroxymethyl)-1-methyl-2-piperidinone | C13H16FNO2 | 详情 | 详情 |