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【结 构 式】

【分子编号】58325

【品名】methyl (3S)-3-(1H-indol-3-yl)butanoate

【CA登记号】

【 分 子 式 】C13H15NO2

【 分 子 量 】217.26764

【元素组成】C 71.87% H 6.96% N 6.45% O 14.73%

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:(VIII)

The reaction of indole-3-carbaldehyde (I) with benzyl chloroformate and NaH in THF gives the carbamate (II), which is condensed with the chiral oxazepinedione (III) by means of TiCl4 and pyridine in THF to yield a mixture of the cis (IV) and trans (V) adducts, which are easily separated by chromatography. The cis (IV) isomer can be thermally isomerized to the desired trans (V) isomer. The diastereoselective methylation of the double bond of (V) by means of MeMgBr in THF affords the methylated adduct (VI), which is hydrolyzed in acidic medium to afford the chiral indolylbutyric acid (VII). The reaction of (VII) with diazomethane provides the corresponding methyl ester (VIII), which is submitted to alpha hydroxylation by means of LDA, O2 and triethyl phosphite in HMPT/THF to give the chiral 2-hydroxy-3-(3-indolyl)butyric acid (IX). The protection of (IX) by means of dihydropyran (DHP) and Ts-OH yields the tetrahydropyranyl diprotected compound (X), which is hydrolyzed with LiOH in THF/water to afford the carboxylic acid (XI). The condensation of (XI) with N-methyl-thiourea (XII) by means of 2-chloro-3-ethylbenzoxazolium tetrafluoroborate (CEBF) and TEA in HMPT/dichloromethane provides a mixture of the S-acylisothiourea (XIII) and N-acylthiourea (XIV), which are easily separated. The S-acyl isomer (XIII) can be rearranged to the desired N-acyl isomer (XIV) by heating in refluxing dioxane. The N-acyl isomer (XIV) is deprotected by means of Ac-OH in THF/water to give the hydroxy derivative (XV), which is finally cyclized by means of CEBF and TEA in acetonitrile to afford the target indolmycin.

1 Takeda, T.; Mukaiyama, T.; Asymmetric total synthesis of indolmycin. Chem Lett 1980, 163.
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) 46797 Indole-3-aldehyde; 3-Formylindole; 1H-Indole-3-carbaldehyde; Indole-3-carboxaldehyde 487-89-8 C9H7NO 详情 详情
(II) 58319 benzyl 3-formyl-1H-indole-1-carboxylate C17H13NO3 详情 详情
(III) 58320 (2R,3S)-3,4-dimethyl-2-phenyl-1,4-oxazepane-5,7-dione C13H15NO3 详情 详情
(IV) 58321 benzyl 3-{[(2R,3S)-3,4-dimethyl-5,7-dioxo-2-phenyl-1,4-oxazepan-6-ylidene]methyl}-1H-indole-1-carboxylate C30H26N2O5 详情 详情
(V) 58323 benzyl 3-{[(2R,3S)-3,4-dimethyl-5,7-dioxo-2-phenyl-1,4-oxazepan-6-ylidene]methyl}-1H-indole-1-carboxylate C30H26N2O5 详情 详情
(VI) 58322 benzyl 3-{(1S)-1-[(2R,3S)-3,4-dimethyl-5,7-dioxo-2-phenyl-1,4-oxazepan-6-yl]ethyl}-1H-indole-1-carboxylate C31H30N2O5 详情 详情
(VII) 58324 (3S)-3-(1H-indol-3-yl)butanoic acid C12H13NO2 详情 详情
(VIII) 58325 methyl (3S)-3-(1H-indol-3-yl)butanoate C13H15NO2 详情 详情
(IX) 58326 methyl (2S,3R)-2-hydroxy-3-(1H-indol-3-yl)butanoate C13H15NO3 详情 详情
(X) 58327 methyl (2S,3R)-3-(1-tetrahydro-2H-pyran-2-yl-1H-indol-3-yl)-2-(tetrahydro-2H-pyran-2-yloxy)butanoate C23H31NO5 详情 详情
(XI) 58328 (2S,3R)-3-(1-tetrahydro-2H-pyran-2-yl-1H-indol-3-yl)-2-(tetrahydro-2H-pyran-2-yloxy)butanoic acid C22H29NO5 详情 详情
(XII) 17283 N-methylthiourea 598-52-7 C2H6N2S 详情 详情
(XIII) 58329 S-[imino(methylamino)methyl] (2S,3R)-3-(1-tetrahydro-2H-pyran-2-yl-1H-indol-3-yl)-2-(tetrahydro-2H-pyran-2-yloxy)butanethioate C24H33N3O4S 详情 详情
(XIV) 58330 N-methyl-N'-[(2S,3R)-3-(1-tetrahydro-2H-pyran-2-yl-1H-indol-3-yl)-2-(tetrahydro-2H-pyran-2-yloxy)butanoyl]thiourea C24H33N3O4S 详情 详情
(XV) 58331 N-[(2S,3R)-2-hydroxy-3-(1H-indol-3-yl)butanoyl]-N'-methylthiourea C14H17N3O2S 详情 详情
Extended Information