tert-butyl (1R)-1-(3-fluoro-4-nitrophenyl)-2-hydroxyethylcarbamate -Drug Synthesis Database

【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 合成路线2

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).

参考文献中间体

合成目标

【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).

参考文献中间体

合成目标

【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	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