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【结 构 式】

【分子编号】48302

【品名】N-(2,2-dimethoxyethyl)-N-(1-formylvinyl)acetamide

【CA登记号】

【 分 子 式 】C9H15NO4

【 分 子 量 】201.22244

【元素组成】C 53.72% H 7.51% N 6.96% O 31.8%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(V)

The condensation of 2,2-dimethyl-1,3-dioxan-5-one (I) with aminoacetaldehyde dimethyl acetal (II) followed by acetylation with Ac2O/Et3N afforded the amido dioxin (III). Retro Diels-Alder reaction of dioxin (III) in warm benzonitrile generated the amidoacrolein (V), which was trapped in situ with the silyloxydiene (IV) to yield the cycloadduct (VI). Aldol cyclization between the acetamide and aldehyde functionalities of (VI) in the presence of t-BuOK produced the spiro lactam (VII). Subsequent aldol condensation between the acetal and silyl enolate functions of (VII) under acidic conditions furnished the tricyclic hydroxy ketone (VIII). Reduction of the keto group of (VIII) with NaBH(OAc)3 produced the C-4 axial alcohol (IX). Silylation of both hydroxyl groups of (IX) followed by selective cleavage of the C-2 silyl ether provided the C-4 mono silylated derivative (X). The free C-2 hydroxyl group of (X) was then oxidized to the corresponding ketone (XI) under Swern conditions. The potassium enolate of (XI) was stereoselectively alkylated with p-methoxybenzyl bromide (XII) to yield (XIII). Reduction of the keto group of (XIII) with Red-Al gave rise to the alcohol (XIV) in the undesired equatorial configuration. Inversion of the C-2 stereogenic center of (XIV) was achieved via formation of the sulfonate ester (XVI) with 4-nitrobenzenesulfonyl chloride (XV).

1 Maeng, J.-H.; Funk, R.L.; Total synthesis of the immunosuppressant FR901483 via an amidoacrolein cycloaddition. Org Lett 2001, 3, 8, 1125.
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) 46538 2,2-dimethyl-1,3-dioxan-5-one C6H10O3 详情 详情
(II) 34158 aminoacetaldehyde dimethylacetal; 2,2-dimethoxy-1-ethanamine; 2,2-dimethoxyethylamine 22483-09-6 C4H11NO2 详情 详情
(III) 48300 N-(2,2-dimethoxyethyl)-N-(2,2-dimethyl-4H-1,3-dioxin-5-yl)acetamide C12H21NO5 详情 详情
(IV) 48301 triisopropyl[(1-methylene-2-propenyl)oxy]silane; 1-methylene-2-propenyl triisopropylsilyl ether C13H26OSi 详情 详情
(V) 48302 N-(2,2-dimethoxyethyl)-N-(1-formylvinyl)acetamide C9H15NO4 详情 详情
(VI) 48303 N-(2,2-dimethoxyethyl)-N-[1-formyl-4-[(triisopropylsilyl)oxy]-3-cyclohexen-1-yl]acetamide C22H41NO5Si 详情 详情
(VII) 48304 1-(2,2-dimethoxyethyl)-8-[(triisopropylsilyl)oxy]-1-azaspiro[4.5]deca-3,7-dien-2-one C22H39NO4Si 详情 详情
(VIII) 48305 (1S,7R,8R)-7-hydroxy-5-azatricyclo[6.3.1.0(1,5)]dodec-2-ene-4,9-dione C11H13NO3 详情 详情
(IX) 48306 (1S,7R,8S,9S)-7,9-dihydroxy-5-azatricyclo[6.3.1.0(1,5)]dodec-2-en-4-one C11H15NO3 详情 详情
(X) 48307 (1S,7R,8R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-5-azatricyclo[6.3.1.0(1,5)]dodec-2-en-4-one C17H29NO3Si 详情 详情
(XI) 48308 (1S,8S,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-azatricyclo[6.3.1.0(1,5)]dodec-2-ene-4,7-dione C17H27NO3Si 详情 详情
(XII) 27490 1-(bromomethyl)-4-methoxybenzene C8H9BrO 详情 详情
(XIII) 48309 (1S,6S,8S,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-2-ene-4,7-dione C25H35NO4Si 详情 详情
(XIV) 48310 (1S,6S,7R,8R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-2-en-4-one C25H37NO4Si 详情 详情
(XV) 15809 4-nitrobenzenesulfonyl chloride 98-74-8 C6H4ClNO4S 详情 详情
(XVI) 48311 (1S,6S,7R,8S,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-6-(4-methoxybenzyl)-4-oxo-5-azatricyclo[6.3.1.0(1,5)]dodec-2-en-7-yl 4-nitrobenzenesulfonate C31H40N2O8SSi 详情 详情
Extended Information