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【结 构 式】

【分子编号】62505

【品名】1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone

【CA登记号】

【 分 子 式 】C18H30O2Si

【 分 子 量 】306.5205

【元素组成】C 70.53% H 9.86% O 10.44% Si 9.16%

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)

4-Hydroxypropiophenone (I) was protected as the triisopropylsilyl ether (II) and subsequently brominated with elemental bromine in CCl4 . The resultant bromo ketone (III) was subsequently coupled with 4-hydroxy-4-phenylpiperidine (IV) to afford the racemic amino ketone (V). This was stereoselectively reduced with NaBH4 in EtOH yielding the threo-amino alcohol (VI). Then, desilylation of (VI) with tetrabutylammonium fluoride furnished the racemic phenol compound. Resolution into the enantiomers has been reported by formation of the corresponding D-tartaric acid salts

1 Chenard, B.L.; et al.; (1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol: A potent new neuroprotectant which blocks N-methyl-D-aspartate responses. J Med Chem 1995, 38, 16, 3138.
2 Chenard, B.L. (Pfizer Inc.); 2-Piperidino-1-alkanol derivs. as antiischemic agents. US 5272160 .
3 Walinsky, S.W.; Rainville, J.P.; Sinay, T.G. Jr. (Pfizer Products Inc.); Process for the preparation of the mesylate salt trihydrate of 1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol. EP 1151995 .
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) 58982 4'-Hydroxypropiophenone; 4-Hydroxypropiophenone; Ethyl 4-Hydroxyphenyl ktone; p-Hydroxypropiophenone; Paroxypropione 70-70-2 C9H10O2 详情 详情
(II) 62505 1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone C18H30O2Si 详情 详情
(III) 62506 2-bromo-1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone C18H29BrO2Si 详情 详情
(IV) 28021 4-phenyl-4-piperidinol; 4-Hydroxy-4-phenylpiperidine; 4-(4-Phenyl)-4-hydroxypiperidine 40807-61-2 C11H15NO 详情 详情
(V) 62507 2-(4-hydroxy-4-phenyl-1-piperidinyl)-1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone C29H43NO3Si 详情 详情
(VI) 62508 1-((1S,2S)-2-hydroxy-1-methyl-2-{4-[(triisopropylsilyl)oxy]phenyl}ethyl)-4-phenyl-4-piperidinol C29H45NO3Si 详情 详情

合成路线2

该中间体在本合成路线中的序号:(II)

4-Hydroxypropiophenone (I) was protected as the triisopropylsilyl ether (II) and subsequently brominated with elemental bromine in CCl4. The resultant bromo ketone (III) was subsequently coupled with 4-hydroxy-4-phenylpiperidine (IV) to afford the racemic amino ketone (V). This was stereoselectively reduced with NaBH4 in EtOH yielding the threo-amino alcohol (VI). Then, desilylation of (VI) with tetrabutylammonium fluoride furnished the racemic phenol compound. Resolution into the enantiomers has been reported by formation of the corresponding D-tartaric acid salts. Finally, the title product was obtained by dissolving D-(-)-tartaric salt (VII) in water in the presence of methanesulfonic acid

1 Chenard, B.L.; et al.; (1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol: A potent new neuroprotectant which blocks N-methyl-D-aspartate responses. J Med Chem 1995, 38, 16, 3138.
2 Chenard, B.L. (Pfizer Inc.); 2-Piperidino-1-alkanol derivs. as antiischemic agents. US 5272160 .
3 Walinsky, S.W.; Rainville, J.P.; Sinay, T.G. Jr. (Pfizer Products Inc.); Process for the preparation of the mesylate salt trihydrate of 1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol. EP 1151995 .
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) 58982 4'-Hydroxypropiophenone; 4-Hydroxypropiophenone; Ethyl 4-Hydroxyphenyl ktone; p-Hydroxypropiophenone; Paroxypropione 70-70-2 C9H10O2 详情 详情
(II) 62505 1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone C18H30O2Si 详情 详情
(III) 62506 2-bromo-1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone C18H29BrO2Si 详情 详情
(IV) 28021 4-phenyl-4-piperidinol; 4-Hydroxy-4-phenylpiperidine; 4-(4-Phenyl)-4-hydroxypiperidine 40807-61-2 C11H15NO 详情 详情
(V) 62507 2-(4-hydroxy-4-phenyl-1-piperidinyl)-1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone C29H43NO3Si 详情 详情
(VI) 62508 1-((1S,2S)-2-hydroxy-1-methyl-2-{4-[(triisopropylsilyl)oxy]phenyl}ethyl)-4-phenyl-4-piperidinol C29H45NO3Si 详情 详情
(VII) 62509 1-[(1S,2S)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]-4-phenyl-4-piperidinol C20H25NO3 详情 详情
Extended Information