【结 构 式】 |
【分子编号】57988 【品名】methyl (6S)-6,8-dichlorooctanoate 【CA登记号】 |
【 分 子 式 】C9H16Cl2O2 【 分 子 量 】227.13024 【元素组成】C 47.59% H 7.1% Cl 31.22% O 14.09% |
合成路线1
该中间体在本合成路线中的序号:(LXII)Both enantiomers of racemic 8-chloro-6-hydroxyoctanoic acid (LX) were separated employing either (+)- or (-)-alpha-methylbenzylamine. Esterification of the (R)-(-)-enantiomer with HCl-MeOH provided the chloro hydroxy ester (LXI). Further chlorination of (LXI) with SOCl2 and pyridine proceeded with inversion of configuration at C-6 to furnish the (S)-dichloro derivative (LXII). The cyclic disulfide (L) was then prepared by treatment of chloride (LXII) with sulfur and sodium sulfide in boiling EtOH. Basic hydrolysis of the methyl ester group of (LXII) then afforded (R) alpha lipoic acid. The title compound was also obtained from the (S)-(+)-acid (LXIII). Reaction of hydroxy acid (LXIII) with methanesulfonyl chloride produced the chloro mesylate (LXIV), which was then cyclized to the target disulfide in the presence of sulfur and Na2S.
【2】 Villani, F.; Nardi, A.; Salvi, A.; Falabella, G.; Synthesis of R(+)alpha-lipoic acid. WO 0230919 . |
【1】 Laban, G.; Beisswenger, T.; Gewald, R. (AWD.pharma GmbH & Co. KG); Preparation and use of the pure enantiomers of 8-chloro-6-sulfonyloxy-octanoic acid and its alkyl esters and of the pure enantiomers of 6,8-dichloro-octanoic acid and its alkyl esters. DE 19533881; EP 0763533; US 5731448 . |
【3】 Laban, G.; Beisswenger, T.; Gewald, R. (AWD.pharma GmbH & Co. KG); Preparation and utilisation of pure enantiomers of 8-halogen-6-hydroxyoctanoic acid, their alkyl esters and their salts with pure enantiomers of alpha-methyl-benzylamines. DE 19533882; EP 0763516; US 5869713 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(L) | 57976 | methyl 5-[(3R)-1,2-dithiolan-3-yl]pentanoate | C9H16O2S2 | 详情 | 详情 | |
(LX) | 57985 | 8-chloro-6-hydroxyoctanoic acid | C8H15ClO3 | 详情 | 详情 | |
(LXI) | 57986 | methyl (6R)-8-chloro-6-hydroxyoctanoate | C9H17ClO3 | 详情 | 详情 | |
(LXII) | 57988 | methyl (6S)-6,8-dichlorooctanoate | C9H16Cl2O2 | 详情 | 详情 | |
(LXIII) | 57987 | (6S)-8-chloro-6-hydroxyoctanoic acid | C8H15ClO3 | 详情 | 详情 | |
(LXIV) | 57989 | (6S)-8-chloro-6-[(methylsulfonyl)oxy]octanoic acid | C9H17ClO5S | 详情 | 详情 |