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【结 构 式】 
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【分子编号】12650 【品名】4-[4-Morpholinyl(3-nitrophenyl)methyl]morpholine 【CA登记号】 |
【 分 子 式 】C15H21N3O4 【 分 子 量 】307.34956 【元素组成】C 58.62% H 6.89% N 13.67% O 20.82% |
合成路线1
该中间体在本合成路线中的序号：(II)A new synthesis for (4S)-efonidipine has been described: The reaction of 5,5-dimethyl-2-(2-oxopropyl)-1,3,2-dioxaphosphorinan-2-one (I) with dimorpholino(3-nitrophenyl)methane (II) by means of trifluoroacetic acid in hot toluene gives 5,5-dimethyl-2-[1-acetyl-2-(3-nitrophenyl)vinyl]-1,3,2-dioxaphosphorina n-2-one (III), which is cyclized with 3-aminocrotonic acid 2(S)-methoxy-2-phenylethyl ester (IV) in refluxing toluene; the recrystallization of the resulting product affords 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4(S)-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid 2(S)-methoxy-2-phenylethyl ester (V). The protection of the NH group of (V) with chloromethyl methyl ether and NaH in THF yields the N-methoxymethyl derivative (VI), which is transesterified with 2-(N-benzyl-N-methylamino)ethanol (VII) and NaH in DMSO, giving the protected final product (VIII). Finally, this compound is deprotected with HCl in ethanol.
| 【1】 Seto, K.; Matsumoto, H.; Sakoda, R.; Synthesis and crystal structure of optically active 2-[benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate (NZ-105). Chem Pharm Bull 1992, 40, 9, 2377. |
| 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) | 12645 | 5,5-Dimethyl-2-(2-oxopropyl)-1,3,2lambda(5)-dioxaphosphinan-2-one | C8H15O4P | 详情 | 详情 | |
| (II) | 12650 | 4-[4-Morpholinyl(3-nitrophenyl)methyl]morpholine | C15H21N3O4 | 详情 | 详情 | |
| (III) | 12647 | 2-[(Z)-1-Acetyl-2-(3-nitrophenyl)ethenyl]-5,5-dimethyl-1,3,2lambda(5)-dioxaphosphinan-2-one | C15H18NO6P | 详情 | 详情 | |
| (IV) | 12652 | (2S)-2-methoxy-2-phenylethyl (E)-3-amino-2-butenoate | C13H17NO3 | 详情 | 详情 | |
| (V) | 12653 | (2S)-2-methoxy-2-phenylethyl (4S)-5-(5,5-dimethyl-2-oxo-1,3,2lambda(5)-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate | C28H33N2O8P | 详情 | 详情 | |
| (VI) | 12654 | (2S)-2-methoxy-2-phenylethyl (4S)-5-(5,5-dimethyl-2-oxo-1,3,2lambda(5)-dioxaphosphinan-2-yl)-1-(methoxymethyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate | C30H37N2O9P | 详情 | 详情 | |
| (VII) | 12655 | 2-(Benzylanilino)-1-ethanol | C15H17NO | 详情 | 详情 | |
| (VIII) | 12656 | 2-(benzylanilino)ethyl (4S)-5-(5,5-dimethyl-2-oxo-1,3,2lambda(5)-dioxaphosphinan-2-yl)-1-(methoxymethyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate | C36H42N3O8P | 详情 | 详情 |