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【结 构 式】 
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【分子编号】33810 【品名】ethyl (2S,3R,4S)-2-(2,2-dimethylpentyl)-4-(7-methoxy-1,3-benzodioxol-5-yl)-3-pyrrolidinecarboxylate 【CA登记号】 |
【 分 子 式 】C22H33NO5 【 分 子 量 】391.50776 【元素组成】C 67.49% H 8.5% N 3.58% O 20.43% |
合成路线1
该中间体在本合成路线中的序号：(Va)Condensation of ketoester (I) with nitrovinyl benzodioxole (II) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene gave adduct (III). Hydrogenation of the nitro group of (III) over Raney Nickel with concomitant cyclization yielded dihydropyrrole (IV). Further reduction of (IV) with sodium cyanoborohydride provided a mixture of diastereomeric pyrrolidines. Chromatographic separation removed the cis,cis isomer, affording a mixture of trans,trans and cis,trans products (V). N-Alkylation of the pyrrolidine (V) with N,N-dibutyl bromoacetamide (VI) furnished (VIIa-b). Finally, selective hydrolysis of the ester group from the trans,trans isomer produced a mixture of cis,trans ester (VIII) and the target trans,trans acid, which were readily separated by fractional extraction.
| 【1】 Winn, M.; Boyd, S.A.; Hutchins, C.W.; Tasker, A.S.; Von Geldern, T.W.; Kester, J.A.; Sorensen, B.K.; Szczepankiewicz, B.G.; Henry, K.J. Jr.; Liu, G.; Wittenberger, S.J.; King, S.A. (Abbott Laboratories Inc.); Novel benzo-1,3-dioxolyl- and benzofuranyl substd. pyrrolidine derivs. as endothelin antagonists. EP 0885215; WO 9730045 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Va) | 33810 | ethyl (2S,3R,4S)-2-(2,2-dimethylpentyl)-4-(7-methoxy-1,3-benzodioxol-5-yl)-3-pyrrolidinecarboxylate | C22H33NO5 | 详情 | 详情 | |
| (Vb) | 33811 | ethyl (2R,3R,4S)-2-(2,2-dimethylpentyl)-4-(7-methoxy-1,3-benzodioxol-5-yl)-3-pyrrolidinecarboxylate | C22H33NO5 | 详情 | 详情 | |
| (VIIa) | 33812 | ethyl (2S,3R,4S)-1-[2-(dibutylamino)-2-oxoethyl]-2-(2,2-dimethylpentyl)-4-(7-methoxy-1,3-benzodioxol-5-yl)-3-pyrrolidinecarboxylate | C32H52N2O6 | 详情 | 详情 | |
| (VIIb),(VIII) | 33813 | ethyl (2R,3R,4S)-1-[2-(dibutylamino)-2-oxoethyl]-2-(2,2-dimethylpentyl)-4-(7-methoxy-1,3-benzodioxol-5-yl)-3-pyrrolidinecarboxylate | C32H52N2O6 | 详情 | 详情 | |
| (I) | 33806 | ethyl 5,5-dimethyl-3-oxooctanoate | C12H22O3 | 详情 | 详情 | |
| (II) | 33807 | 4-methoxy-6-[(E)-2-nitroethenyl]-1,3-benzodioxole; methyl 6-[(E)-2-nitroethenyl]-1,3-benzodioxol-4-yl ether | C10H9NO5 | 详情 | 详情 | |
| (III) | 33808 | ethyl 2-[1-(7-methoxy-1,3-benzodioxol-5-yl)-2-nitroethyl]-5,5-dimethyl-3-oxooctanoate | C22H31NO8 | 详情 | 详情 | |
| (IV) | 33809 | ethyl 2-(2,2-dimethylpentyl)-4-(7-methoxy-1,3-benzodioxol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxylate | C22H31NO5 | 详情 | 详情 | |
| (VI) | 20685 | 2-Bromo-N,N-dibutylacetamide; N,N-Dibutylbromoacetamide | C10H20BrNO | 详情 | 详情 |