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【结 构 式】

【分子编号】32516

【品名】4-(7-methoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)butyric acid

【CA登记号】

【 分 子 式 】C15H18O4

【 分 子 量 】262.30552

【元素组成】C 68.69% H 6.92% O 24.4%

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:(V)

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:(V)

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
Extended Information