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【结 构 式】

【分子编号】40552

【品名】tert-butyl (1R)-1-(3-fluoro-4-nitrophenyl)-2-hydroxyethylcarbamate

【CA登记号】

【 分 子 式 】C13H17FN2O5

【 分 子 量 】300.2868632

【元素组成】C 52% H 5.71% F 6.33% N 9.33% O 26.64%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(II)

The dipeptide intermediate (XI) has been obtained as follows: The coupling of the two synthons (I) and (II) by means of K2CO3 and 18-C-6 in DMSO gives the diphenyl ether (III), which is reduced at its nitro group with H2 over Pd/C yielding the amine (IV). The treatment of (IV) with tert-butyl nitrite, HBF4 and Cu2O affords the phenol (V), which is methylated with MeI and K2CO3 to provide the corresponding methyl ether (VI). The protection of the primary alcohol of (VI) with benzyl bromide (A) and K2CO3 gives the benzyl ether (VII), which is deprotected at the Mem and trifluoroacetamido groups yielding the aminoethanol derivative (VIII). The condensation of (VIII) with the protected phenylalanine derivative (IX) by means of EDC and HOBT affords the corresponding amide (X), which is finally oxidized with Dess Martin periodinane (DMP) and NaClO2 to afford the desired dipeptide 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.
2 Boger, D.L.; et al.; Total synthesis of the teicoplanin aglycon. J Am Chem Soc 2000, 122, 30, 7416.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 12912 1-(Bromomethyl)benzene; Alpha-bromotoluene 100-39-0 C7H7Br 详情 详情
(I) 40551 2,2,2-trifluoro-N-[(1S)-1-(3-hydroxy-5-methoxyphenyl)-2-[(2-methoxyethoxy)methoxy]ethyl]acetamide C15H20F3NO6 详情 详情
(II) 40552 tert-butyl (1R)-1-(3-fluoro-4-nitrophenyl)-2-hydroxyethylcarbamate C13H17FN2O5 详情 详情
(III) 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
(IV) 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
(V) 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
(VI) 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
(VII) 40557 tert-butyl (1R)-2-(benzyloxy)-1-[4-methoxy-3-(3-methoxy-5-[(1S)-2-[(2-methoxyethoxy)methoxy]-1-[(2,2,2-trifluoroacetyl)amino]ethyl]phenoxy)phenyl]ethylcarbamate C36H45F3N2O10 详情 详情
(VIII) 40558 tert-butyl (1R)-1-(3-[3-[(1S)-1-amino-2-hydroxyethyl]-5-methoxyphenoxy]-4-methoxyphenyl)-2-(benzyloxy)ethylcarbamate C30H38N2O7 详情 详情
(IX) 40559 (2R)-3-(4-fluoro-3-nitrophenyl)-2-(propionylamino)propionic acid C12H13FN2O5 详情 详情
(X) 40560 tert-butyl (1R)-2-(benzyloxy)-1-[3-[3-((1S)-1-[[(2R)-3-(4-fluoro-3-nitrophenyl)-2-(propionylamino)propanoyl]amino]-2-hydroxyethyl)-5-methoxyphenoxy]-4-methoxyphenyl]ethylcarbamate C42H49FN4O11 详情 详情
(XI) 40561 (2S)-2-[3-(5-[(1R)-2-(benzyloxy)-1-[(tert-butoxycarbonyl)amino]ethyl]-2-methoxyphenoxy)-5-methoxyphenyl]-2-[[(2R)-3-(4-fluoro-3-nitrophenyl)-2-(propionylamino)propanoyl]amino]ethanoic acid C42H47FN4O12 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

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
Extended Information