【结 构 式】 |
【分子编号】69237 【品名】(3R,4R)-benzyl 3-acetoxy-4-azidopyrrolidine-1-carboxylate 【CA登记号】 |
【 分 子 式 】C14H16N4O4 【 分 子 量 】304.3056 【元素组成】C 55.26% H 5.3% N 18.41% O 21.03% |
合成路线1
该中间体在本合成路线中的序号:(XLIV)Intermediate (XXXVIII) can be prepared by several alternative methods. Protection of diallylamine (XXXIX) with benzyl chloroformate and Et3N in CH2Cl2 yields the benzyloxycarbonyl derivative (XL), which undergoes ring-closing metathesis in the presence of Grubbs’ catalyst to give 1-Cbz-3-pyrroline (XLI). Reaction of compound (XLI) with NBS in aqueous DMSO followed by treatment of the resulting bromohydrin with 1 N NaOH leads to epoxide (XLII), which undergoes ring opening with NaN3 in aqueous dioxane to afford the racemic trans-azidoalcohol (XLIII). Resolution of rac-(XLIII) is then effected by incubation with lipase PS in the presence of vinyl acetate in i-Pr2O to give the (R,R)-acetate (XLIV) along with unreacted (S,S)-alcohol (XLIII). Methylation of (S,S)-alcohol (XLIII) with iodomethane and NaH affords ether (XLV), which is submitted to azide group reduction by means of PPh3 in THF/H2O to give amine (XLVI). Protection of amine (XLVI) with Boc2O and Et3N followed by selective removal of the Cbz group in the resulting bis-carbamate (XLVII) using poly(methylhydrosiloxane) and Pd/C in EtOH leads to the pyrrolidine (XLVIII), which is finally treated with Boc2O and Et3N .
【1】 Kamal, A., Shaik, A.A., Sandbhor, M., Malik, M.S., Kaga, H. Chemoenzymatic synthesis of (3S,4S)- and (3R,4R)-3-methoxy-4-methylaminopyrrolidine. Tetrahedron Lett 2004, 45(43): 8057-9. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XXXVIII) | 69233 | (3S,4S)-tert-butyl 3-((tert-butoxycarbonyl)amino)-4-methoxypyrrolidine-1-carboxylate | C15H28N2O5 | 详情 | 详情 | |
(XXXIX) | 68044 | diallylamine;Di-2-propenylamine;N-2-Propenyl-2-propen-1-amine | 124-02-7 | C6H11N | 详情 | 详情 |
(XL) | 69234 | benzyl diallylcarbamate | C14H17NO2 | 详情 | 详情 | |
(XLI) | 15923 | 1-Benzyloxycarbonyl-3-pyrroline;3-Pyrroline-1-carboxylicacid, benzyl ester ;N-(Benzyloxycarbonyl)-3-pyrroline;Benzyl 3-pyrroline-1-carboxylate;2H,5H-Pyrrole-1-carboxylicacid benzyl ester;2,5-Dihydropyrrole-1-carboxylic acid benzyl ester;benzyl 2,5-dihydro-1H-pyrrole-1-carboxylate | 31970-04-4 | C12H13NO2 | 详情 | 详情 |
(XLII) | 69235 | benzyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate | C12H13NO3 | 详情 | 详情 | |
(XLIII) | 69236 | (3S,4S)-benzyl 3-azido-4-hydroxypyrrolidine-1-carboxylate-benzyl 3-azido-4-hydroxypyrrolidine-1-carboxylate | C12H14N4O3 | 详情 | 详情 | |
(XLIV) | 69237 | (3R,4R)-benzyl 3-acetoxy-4-azidopyrrolidine-1-carboxylate | C14H16N4O4 | 详情 | 详情 | |
(XLV) | 69238 | (3S,4S)-benzyl 3-azido-4-methoxypyrrolidine-1-carboxylate | C13H16N4O3 | 详情 | 详情 | |
(XLVI) | 69241 | (3S,4S)-benzyl 3-amino-4-methoxypyrrolidine-1-carboxylate | C13H18N2O3 | 详情 | 详情 | |
(XLVII) | 69239 | (3S,4S)-benzyl 3-((tert-butoxycarbonyl)amino)-4-methoxypyrrolidine-1-carboxylate | C18H26N2O5 | 详情 | 详情 | |
(XLVIII) | 69240 | tert-butyl ((3S,4S)-4-methoxypyrrolidin-3-yl)carbamate | C10H20N2O3 | 详情 | 详情 |