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【结 构 式】

【分子编号】38667

【品名】(1S,3R,7S,8S,8aR)-8-[(3R,5R)-7-(butylamino)-3,5-dihydroxy-7-oxoheptyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2,2-dimethylbutanoate

【CA登记号】

【 分 子 式 】C29H49NO5

【 分 子 量 】491.7118

【元素组成】C 70.84% H 10.04% N 2.85% O 16.27%

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:(V)

The reaction of Lovastatin (I) with refluxing butylamine gives the N-butylamide (II), which is silylated with TBDMS-Cl and imidazole to yield the bis(silyl) ether (III). The careful methylation of (III) with MeI (only 1.5 mol) and lithium pyrrolidide in THF at -10 C affords a high yield of 2,2-dimethylbutyrate (IV) avoiding the methylation of the amide nitrogen. The desilylation of (IV) with MsOH in methanol gives the dihydroxyamide (V), which is treated successively with NaOH in methanol/water, with HCl, and finally with ammonia in methanol to give the ammonium salt (VI). Finally, this compound is cyclized by heating at 100 C in toluene to afford the target simvastatin.

1 Askin, D.; et al.; Synthesis of synvinolin: Extremely high conversion alkylation of an ester enolate. J Org Chem 1991, 56, 16, 4929.
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) 64415 (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate C24H36O5 详情 详情
(II) 38664 (1S,3R,7S,8S,8aR)-8-[(3R,5R)-7-(butylamino)-3,5-dihydroxy-7-oxoheptyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate C28H47NO5 详情 详情
(III) 38665 (1S,3R,7S,8S,8aR)-8-((3R,5R)-7-(butylamino)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-7-oxoheptyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate C40H75NO5Si2 详情 详情
(IV) 38666 (1S,3R,7S,8S,8aR)-8-((3R,5R)-7-(butylamino)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-7-oxoheptyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2,2-dimethylbutanoate C41H77NO5Si2 详情 详情
(V) 38667 (1S,3R,7S,8S,8aR)-8-[(3R,5R)-7-(butylamino)-3,5-dihydroxy-7-oxoheptyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2,2-dimethylbutanoate C29H49NO5 详情 详情
(VI) 37616 ammonium (3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-[(2,2-dimethylbutanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydro-1-naphthalenyl]-3,5-dihydroxyheptanoate C25H43NO6 详情 详情
Extended Information