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【结 构 式】 
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【分子编号】32514 【品名】ethyl 7-methoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenecarboxylate 【CA登记号】 |
【 分 子 式 】C14H16O4 【 分 子 量 】248.27864 【元素组成】C 67.73% H 6.5% O 25.78% |
合成路线1
该中间体在本合成路线中的序号：(II)Condensation of 7-methoxytetralone (I) with diethyl carbonate in the presence of NaH afforded ketoester (II), which was alkylated with ethyl 4-bromobutyrate (III) to give (IV). Hydrolysis and decarboxylation of (IV) using KOH in boiling MeOH provided ketoacid (V). Subsequent addition of thiophenol to (V) with concomitant esterification in the presence of ethanolic HCl, followed by oxidative aromatization with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gave rise to the (phenylthio)naphthalene (VI). Addition of methylmagnesium bromide to the ester function of (VI) yielded carbinol (VII), which was cyclized to the tetrahydroanthracene (VIII) employing ethereal H2SO4. After reductive removal of the phenylthio group of (VIII) by means of Raney Ni yielding (IX), its methyl ether group was cleaved with BBr3, providing phenol (X). Treatment with trifluoromethanesulfonic anhydride gave triflate (XI).
| 【1】 Ericsson, A.; Marinier, A.; Lapointe, P.; et al.; Synthesis and SAR of novel dihydroanthracene derivatives as retinoid analogs. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 43. |
| 【2】 Starrett, J.E. Jr.; Tramposch, K.M.; Martel, A.; Nair, X.; Zusi, F.C.; Reczek, P.R.; Marinier, A.; Ericsson, A. (Bristol-Myers Squibb Co.); Retinoid-like cpds.. WO 9849136 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12951 | Benzenethiol; Phenylmercaptan; Phenylhydrosulfide | 108-98-5 | C6H6S | 详情 | 详情 | |
| (I) | 21385 | 7-methoxy-3,4-dihydro-1(2H)-naphthalenone | 6836-19-7 | C11H12O2 | 详情 | 详情 |
| (II) | 32514 | ethyl 7-methoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenecarboxylate | C14H16O4 | 详情 | 详情 | |
| (III) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
| (IV) | 32515 | ethyl 2-(4-ethoxy-4-oxobutyl)-7-methoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenecarboxylate | C20H26O6 | 详情 | 详情 | |
| (V) | 32516 | 4-(7-methoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)butyric acid | C15H18O4 | 详情 | 详情 | |
| (VI) | 32517 | ethyl 4-[7-methoxy-1-(phenylsulfanyl)-2-naphthyl]butanoate | C23H24O3S | 详情 | 详情 | |
| (VII) | 32518 | 5-[7-methoxy-1-(phenylsulfanyl)-2-naphthyl]-2-methyl-2-pentanol | C23H26O2S | 详情 | 详情 | |
| (VIII) | 32519 | 5,5-dimethyl-9-(phenylsulfanyl)-5,6,7,8-tetrahydro-2-anthracenyl methyl ether; 6-methoxy-1,1-dimethyl-10-(phenylsulfanyl)-1,2,3,4-tetrahydroanthracene | C23H24OS | 详情 | 详情 | |
| (IX) | 32520 | 5,5-dimethyl-5,6,7,8-tetrahydro-2-anthracenyl methyl ether; 6-methoxy-1,1-dimethyl-1,2,3,4-tetrahydroanthracene | C17H20O | 详情 | 详情 | |
| (X) | 32521 | 5,5-dimethyl-5,6,7,8-tetrahydro-2-anthracenol | C16H18O | 详情 | 详情 | |
| (XI) | 32522 | 5,5-dimethyl-5,6,7,8-tetrahydro-2-anthracenyl trifluoromethanesulfonate | C17H17F3O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Condensation of 7-methoxytetralone (I) with diethyl carbonate in the presence of NaH afforded ketoester (II), which was alkylated with ethyl 4-bromobutyrate (III) to give (IV). Hydrolysis and decarboxylation of (IV) using KOH in boiling MeOH provided ketoacid (V). Subsequent addition of thiophenol to (V) with concomitant esterification in the presence of ethanolic HCl, followed by oxidative aromatization with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gave rise to the (phenylthio)naphthalene (VI). Addition of methylmagnesium bromide to the ester function of (VI) yielded carbinol (VII), which was cyclized to the tetrahydroanthracene (VIII) employing ethereal H2SO4. After reductive removal of the phenylthio group of (VIII) by means of Raney-Ni yielding (IX), its methyl ether group was cleaved with BBr3, providing phenol (X). Treatment with trifluoromethanesulfonic anhydride gave triflate (XI).
| 【1】 Ericsson, A.; Marinier, A.; Lapointe, P.; et al.; Synthesis and SAR of novel dihydroanthracene derivatives as retinoid analogs. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 43. |
| 【2】 Starrett, J.E. Jr.; Tramposch, K.M.; Martel, A.; Nair, X.; Zusi, F.C.; Reczek, P.R.; Marinier, A.; Ericsson, A. (Bristol-Myers Squibb Co.); Retinoid-like cpds.. WO 9849136 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12951 | Benzenethiol; Phenylmercaptan; Phenylhydrosulfide | 108-98-5 | C6H6S | 详情 | 详情 | |
| (I) | 21385 | 7-methoxy-3,4-dihydro-1(2H)-naphthalenone | 6836-19-7 | C11H12O2 | 详情 | 详情 |
| (II) | 32514 | ethyl 7-methoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenecarboxylate | C14H16O4 | 详情 | 详情 | |
| (III) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
| (IV) | 32515 | ethyl 2-(4-ethoxy-4-oxobutyl)-7-methoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenecarboxylate | C20H26O6 | 详情 | 详情 | |
| (V) | 32516 | 4-(7-methoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)butyric acid | C15H18O4 | 详情 | 详情 | |
| (VI) | 32517 | ethyl 4-[7-methoxy-1-(phenylsulfanyl)-2-naphthyl]butanoate | C23H24O3S | 详情 | 详情 | |
| (VII) | 32518 | 5-[7-methoxy-1-(phenylsulfanyl)-2-naphthyl]-2-methyl-2-pentanol | C23H26O2S | 详情 | 详情 | |
| (VIII) | 32519 | 5,5-dimethyl-9-(phenylsulfanyl)-5,6,7,8-tetrahydro-2-anthracenyl methyl ether; 6-methoxy-1,1-dimethyl-10-(phenylsulfanyl)-1,2,3,4-tetrahydroanthracene | C23H24OS | 详情 | 详情 | |
| (IX) | 32520 | 5,5-dimethyl-5,6,7,8-tetrahydro-2-anthracenyl methyl ether; 6-methoxy-1,1-dimethyl-1,2,3,4-tetrahydroanthracene | C17H20O | 详情 | 详情 | |
| (X) | 32521 | 5,5-dimethyl-5,6,7,8-tetrahydro-2-anthracenol | C16H18O | 详情 | 详情 | |
| (XI) | 32522 | 5,5-dimethyl-5,6,7,8-tetrahydro-2-anthracenyl trifluoromethanesulfonate | C17H17F3O3S | 详情 | 详情 |