【结 构 式】 |
【分子编号】58075 【品名】(3S)-3-[(methylsulfonyl)oxy]-8-(tetrahydro-2H-pyran-2-yloxy)octyl methanesulfonate 【CA登记号】 |
【 分 子 式 】C15H30O8S2 【 分 子 量 】402.5304 【元素组成】C 44.76% H 7.51% O 31.8% S 15.93% |
合成路线1
该中间体在本合成路线中的序号:(VIII)1,6-Hexanediol (I) was protected as the mono-tetrahydropyranyl ether (II), and the free hydroxyl group was subsequently oxidized to aldehyde (III) under Swern conditions. Reformatskii reaction of aldehyde (III) with the organozinc reagent generated from ethyl bromoacetate yielded the racemic hydroxy ester (IV). The requisite (S)-enantiomer (VI) was obtained via oxidation of (IV) to oxo ester (V) using pyridinium chlorochromate, and then asymmetric hydrogenation in the presence of (S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl dichlororuthenium complex. Oxo ester (V) was also prepared by SnCl2-catalyzed insertion of ethyl diazoacetate into aldehyde (III). The chiral hydroxy ester (VI) was then reduced to diol (VII) by means of NaBH4-CuSO4. After conversion of (VII) to the corresponding dimesylate (VIII), removal of the tetrahydropyranyl protecting group under acidic conditions gave alcohol (IX). This was sequentially oxidized with PCC to aldehyde, and then with Ag2O to furnish the target dimesylate acid intermediate (X).
【1】 Upadhya, T.T.; et al.; Asymmetric dihydroxylation and hydrogenation approaches to the enantioselective synthesis of R-(+)-alpha-lipoic acid. Tetrahedron Lett 2001, 42, 29, 4891. |
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) | 58068 | 1,6 Hexanediol; 1,6-Dihydroxyhexane; Hexamethylene glycol | 629-11-8 | C6H14O2 | 详情 | 详情 |
(II) | 58069 | 6-(tetrahydro-2H-pyran-2-yloxy)-1-hexanol | C11H22O3 | 详情 | 详情 | |
(III) | 58070 | 6-(tetrahydro-2H-pyran-2-yloxy)hexanal | C11H20O3 | 详情 | 详情 | |
(IV) | 58071 | ethyl 3-hydroxy-8-(tetrahydro-2H-pyran-2-yloxy)octanoate | C15H28O5 | 详情 | 详情 | |
(V) | 58072 | ethyl 3-oxo-8-(tetrahydro-2H-pyran-2-yloxy)octanoate | C15H26O5 | 详情 | 详情 | |
(VI) | 58073 | ethyl (3S)-3-hydroxy-8-(tetrahydro-2H-pyran-2-yloxy)octanoate | C15H28O5 | 详情 | 详情 | |
(VII) | 58074 | (3S)-8-(tetrahydro-2H-pyran-2-yloxy)-1,3-octanediol | C13H26O4 | 详情 | 详情 | |
(VIII) | 58075 | (3S)-3-[(methylsulfonyl)oxy]-8-(tetrahydro-2H-pyran-2-yloxy)octyl methanesulfonate | C15H30O8S2 | 详情 | 详情 | |
(IX) | 58076 | (3S)-8-hydroxy-3-[(methylsulfonyl)oxy]octyl methanesulfonate | C10H22O7S2 | 详情 | 详情 | |
(X) | 57949 | (6S)-6,8-bis[(methylsulfonyl)oxy]octanoic acid | C10H20O8S2 | 详情 | 详情 |