2-bromo-1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone -Drug Synthesis Database

【结构式】

【分子编号】62506

【品名】2-bromo-1-{4-[(triisopropylsilyl)oxy]phenyl}-1-propanone

【CA登记号】

【分子式】C₁₈H₂₉BrO₂Si

【分子量】385.41656

【元素组成】C 56.09% H 7.58% Br 20.73% O 8.3% Si 7.29%

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：(III)

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

参考文献中间体

合成目标

【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：(III)

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

参考文献中间体

合成目标

【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