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【结 构 式】 
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【分子编号】47037 【品名】tert-butyl (1R)-1-[3-(3-[(1S)-1-amino-2-[(2-methoxyethoxy)methoxy]ethyl]-5-methoxyphenoxy)-4-methoxyphenyl]-2-hydroxyethylcarbamate 【CA登记号】 |
【 分 子 式 】C27H40N2O9 【 分 子 量 】536.62268 【元素组成】C 60.43% H 7.51% N 5.22% O 26.83% |
合成路线1
该中间体在本合成路线中的序号：(XI)The synthesis of intermediate (XI) as been performed as follows: The reaction of 3-benzyloxy-5-methoxystyrene (I) with K2OsO4(OH)4, (DHQ)2PHAL and BocNClNa gives the hydroxyethyl carbamate (II), which is protected with Mem-Cl, yielding (III). The reductive deprotection of (III) with H2 over Pd/C, followed by reaction with trifluoroacetic anhydride (TFAA), affords the amide (IV), which is condensed with the hydroxyethyl carbamate (V) (obtained by reaction of 3-fluoro-4-nitrostyrene (VI) with K2OsO4(OH)4, (DHQD)2PHAL and BocNClNa) by means of K2CO3, providing the diaryl ether (VII). The reduction of the nitro group of (VII) with H2 over Pd/C gives the corresponding amino group, which is converted into the phenol (IX) by reaction with tBu-ONO, BHF4, Cu2O and Cu(NO3)2. The methylation of the phenol (IX) with MeI and K2CO3 yields the corresponding ether (X), which is finally treated with K2CO3 to eliminate the trifluoroacetyl group, yielding the desired intermediate (XI).
| 【1】 Boger, D.L.; et al.; First and second generation total synthesis of the teicoplanin aglycon. J Am Chem Soc 2001, 123, 9, 1862. |
| 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) | 47033 | 1-(benzyloxy)-3-methoxy-5-vinylbenzene; benzyl 3-methoxy-5-vinylphenyl ether | C16H16O2 | 详情 | 详情 | |
| (II) | 47034 | benzyl (1S)-1-[3-(benzyloxy)-5-methoxyphenyl]-2-hydroxyethylcarbamate | C24H25NO5 | 详情 | 详情 | |
| (III) | 47035 | benzyl (1S)-1-[3-(benzyloxy)-5-methoxyphenyl]-2-[(2-methoxyethoxy)methoxy]ethylcarbamate | C28H33NO7 | 详情 | 详情 | |
| (IV) | 40551 | 2,2,2-trifluoro-N-[(1S)-1-(3-hydroxy-5-methoxyphenyl)-2-[(2-methoxyethoxy)methoxy]ethyl]acetamide | C15H20F3NO6 | 详情 | 详情 | |
| (V) | 40552 | tert-butyl (1R)-1-(3-fluoro-4-nitrophenyl)-2-hydroxyethylcarbamate | C13H17FN2O5 | 详情 | 详情 | |
| (VI) | 47036 | 2-fluoro-1-nitro-4-vinylbenzene | C8H6FNO2 | 详情 | 详情 | |
| (VII) | 40553 | tert-butyl (1R)-2-hydroxy-1-[3-(3-methoxy-5-[(1S)-2-[(2-methoxyethoxy)methoxy]-1-[(2,2,2-trifluoroacetyl)amino]ethyl]phenoxy)-4-nitrophenyl]ethylcarbamate | C28H36F3N3O11 | 详情 | 详情 | |
| (VIII) | 40554 | tert-butyl (1R)-1-[4-amino-3-(3-methoxy-5-[(1S)-2-[(2-methoxyethoxy)methoxy]-1-[(2,2,2-trifluoroacetyl)amino]ethyl]phenoxy)phenyl]-2-hydroxyethylcarbamate | C28H38F3N3O9 | 详情 | 详情 | |
| (IX) | 40555 | tert-butyl (1R)-2-hydroxy-1-[4-hydroxy-3-(3-methoxy-5-[(1S)-2-[(2-methoxyethoxy)methoxy]-1-[(2,2,2-trifluoroacetyl)amino]ethyl]phenoxy)phenyl]ethylcarbamate | C28H37F3N2O10 | 详情 | 详情 | |
| (X) | 40556 | tert-butyl (1R)-2-hydroxy-1-[4-methoxy-3-(3-methoxy-5-[(1S)-2-[(2-methoxyethoxy)methoxy]-1-[(2,2,2-trifluoroacetyl)amino]ethyl]phenoxy)phenyl]ethylcarbamate | C29H39F3N2O10 | 详情 | 详情 | |
| (XI) | 47037 | tert-butyl (1R)-1-[3-(3-[(1S)-1-amino-2-[(2-methoxyethoxy)methoxy]ethyl]-5-methoxyphenoxy)-4-methoxyphenyl]-2-hydroxyethylcarbamate | C27H40N2O9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XI)The synthesis of intermediate (XXI) has been performed as follows: The condensation of 4-fluoro-3-nitrobenzyl bromide (XII) with the chiral dihydropyrazine (XIII) by means of BuLi and CuCN gives the chiral adduct (XIV), which is treated with TFA to yield the 4-fluoro-3-nitro-D- phenylalanine (XV). The N-protection of (XV) with Teoc-Cl gives the N-protected phenylalanine (XVI), which is condensed with the already described intermediate (XI) by means of PyBop to yield the amide (XVII). The oxidation of the primary OH group of (XVII) with DMP and NaClO2 affords the carboxylic acid (XVIII), which is cyclized to the cyclic amide (XIX). The cleavage of he protecting groups of (XIX) with HCl, followed by selective N-protection with Boc2O, provides primary carbinol (XX), which is finally oxidized with DMP and NaClO2 to give the desired carboxylic acid intermediate (XXI).
| 【1】 Boger, D.L.; et al.; First and second generation total synthesis of the teicoplanin aglycon. J Am Chem Soc 2001, 123, 9, 1862. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 47037 | tert-butyl (1R)-1-[3-(3-[(1S)-1-amino-2-[(2-methoxyethoxy)methoxy]ethyl]-5-methoxyphenoxy)-4-methoxyphenyl]-2-hydroxyethylcarbamate | C27H40N2O9 | 详情 | 详情 | |
| (XII) | 47038 | 4-(bromomethyl)-1-fluoro-2-nitrobenzene | C7H5BrFNO2 | 详情 | 详情 | |
| (XIII) | 10296 | (R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine; (3R)-3-Isopropyl-5-methoxy-3,6-dihydro-2-pyrazinyl methyl ether; (2R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine | 109838-85-9 | C9H16N2O2 | 详情 | 详情 |
| (XIV) | 47039 | (2R,5S)-2-(4-fluoro-3-nitrobenzyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine; (3R,6S)-3-(4-fluoro-3-nitrobenzyl)-6-isopropyl-5-methoxy-3,6-dihydro-2-pyrazinyl methyl ether | C16H20FN3O4 | 详情 | 详情 | |
| (XV) | 47040 | (2R)-2-amino-3-(4-fluoro-3-nitrophenyl)propionic acid | C9H9FN2O4 | 详情 | 详情 | |
| (XVI) | 47041 | (2R)-3-(4-fluoro-3-nitrophenyl)-2-([[2-(trimethylsilyl)ethoxy]carbonyl]amino)propionic acid | C15H21FN2O6Si | 详情 | 详情 | |
| (XVII) | 47042 | 2-(trimethylsilyl)ethyl (1R,4S)-4-[3-(5-[(1R)-1-[(tert-butoxycarbonyl)amino]-2-hydroxyethyl]-2-methoxyphenoxy)-5-methoxyphenyl]-1-(4-fluoro-3-nitrobenzyl)-2-oxo-6,8,11-trioxa-3-azadodec-1-ylcarbamate | C42H59FN4O14Si | 详情 | 详情 | |
| (XVIII) | 47043 | (2R)-2-[(tert-butoxycarbonyl)amino]-2-[3-[3-((1S,4R)-4-(4-fluoro-3-nitrobenzyl)-1-[[(2-methoxyethoxy)methoxy]methyl]-10,10-dimethyl-3,6-dioxo-7-oxa-2,5-diaza-10-silaundec-1-yl)-5-methoxyphenoxy]-4-methoxyphenyl]ethanoic acid | C42H57FN4O15Si | 详情 | 详情 | |
| (XIX) | 47044 | tert-butyl (8S,11R,14R)-11-(4-fluoro-3-nitrobenzyl)-5,18-dimethoxy-8-[[(2-methoxyethoxy)methoxy]methyl]-10,13-dioxo-2-oxa-9,12-diazatricyclo[13.3.1.1(3,7)]icosa-1(19),3(20),4,6,15,17-hexaen-14-ylcarbamate | C36H43FN4O12 | 详情 | 详情 | |
| (XX) | 47045 | tert-butyl (8S,11R,14R)-11-(4-fluoro-3-nitrobenzyl)-8-(hydroxymethyl)-5,18-dimethoxy-10,13-dioxo-2-oxa-9,12-diazatricyclo[13.3.1.1(3,7)]icosa-1(19),3(20),4,6,15,17-hexaen-14-ylcarbamate | C32H35FN4O10 | 详情 | 详情 | |
| (XXI) | 47046 | (8S,11R,14R)-14-[(tert-butoxycarbonyl)amino]-11-(4-fluoro-3-nitrobenzyl)-5,18-dimethoxy-10,13-dioxo-2-oxa-9,12-diazatricyclo[13.3.1.1(3,7)]icosa-1(19),3(20),4,6,15,17-hexaene-8-carboxylic acid | C32H33FN4O11 | 详情 | 详情 |