|
【结 构 式】 
|
【分子编号】58017 【品名】(4S)-4-(3-chloropropyl)-2,2-dimethyl-1,3-dioxolane 【CA登记号】 |
【 分 子 式 】C8H15ClO2 【 分 子 量 】178.6586 【元素组成】C 53.78% H 8.46% Cl 19.84% O 17.91% |
合成路线1
该中间体在本合成路线中的序号：(II)(3-Ethylphenyl)cyanamide (III) was prepared by treatment of m-ethylaniline (I) with cyanogen bromide (II) in Et2O. Alkylation of (III) with iodomethane and NaH provided the N-methyl cyanamide (IV). This was finally condensed with 1-naphthylamine hydrochloride (V) by heating at 160 C or in the presence of AlCl3 as the catalyst.
| 【1】 Weber, E.; Keana, J.F.W. (University of Oregon); Tri- and tetra-substd. guanidines and their use as excitatory amino acid antagonists. JP 2002020361; US 5262568; WO 9112797 . |
| 【2】 Durant, G.J.; Nagar, S.S. (CeNeS Pharmaceuticals); Preparation of substd. guanidines. WO 9319042 . |
| 【3】 Reddy, N.L.; et al.; Synthesis and structure-activity studies of N,N'-diarylguanidine derivatives. N-(1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine: A new, selective noncompetitive NMDA receptor antagonist. J Med Chem 1994, 37, 2, 260. |
| 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) | 59208 | 3-Ethylaniline; m-Ethylaniline | 587-02-0 | C8H11N | 详情 | 详情 |
| (II) | 58017 | (4S)-4-(3-chloropropyl)-2,2-dimethyl-1,3-dioxolane | C8H15ClO2 | 详情 | 详情 | |
| (III) | 59209 | 3-ethylphenylcyanamide | C9H10N2 | 详情 | 详情 | |
| (IV) | 59210 | 3-ethylphenyl(methyl)cyanamide | C10H12N2 | 详情 | 详情 | |
| (V) | 59211 | 1-Aminonaphthalene; 1-Naphthylamine; alpha-Naphthylamine | 134-32-7 | C10H9N | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIII)In a related method, keto ester (XX) was prepared by Claisen condensation of the lithium enolate of octyl acetate (XVIII) with 4-chlorobutanoyl chloride (XIX). Reduction of the beta-keto ester (XX) with baker's yeast gave rise to the (S)-alcohol (XXI). Subsequent ester group reduction in (XXI) with LiBH4 furnished diol (XXII), which was protected as the acetonide (XXIII) upon treatment with 2,2-dimethoxypropane under acidic conditions. Displacement of the chloride of (XXIII) with the sodium salt of diethyl malonate afforded the substituted malonate (XXIV). Decarbethoxylation of malonate (XXIV) to mono-ester (XXV) was accomplished employing NaCN in hot DMSO. The target dihydroxy ester (XII) was then obtained by acidic acetonide (XXV) hydrolysis.
| 【1】 Jacobs, H.K.; Gopalan, A.S.; Bakers' yeast reduction of alkyl 6-chloro-3-oxohexanoates: Synthesis of (R)-(+)-alpha-lipoic acid. J Chem Soc - Perkins Trans I 1990, 7, 1897. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 57958 | ethyl (6S)-6,8-dihydroxyoctanoate | C10H20O4 | 详情 | 详情 | |
| (XVIII) | 58013 | octyl acetate | C10H20O2 | 详情 | 详情 | |
| (XIX) | 11265 | 4-Chlorobutanoyl chloride; 4-Chlorobutyric acid chloride | 4635-59-0 | C4H6Cl2O | 详情 | 详情 |
| (XX) | 58014 | octyl 6-chloro-3-oxohexanoate | C14H25ClO3 | 详情 | 详情 | |
| (XXI) | 58015 | octyl (3S)-6-chloro-3-hydroxyhexanoate | C14H27ClO3 | 详情 | 详情 | |
| (XXII) | 58016 | (3S)-6-chloro-1,3-hexanediol | C6H13ClO2 | 详情 | 详情 | |
| (XXIII) | 58017 | (4S)-4-(3-chloropropyl)-2,2-dimethyl-1,3-dioxolane | C8H15ClO2 | 详情 | 详情 | |
| (XXIV) | 58018 | diethyl 2-{3-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]propyl}malonate | C15H26O6 | 详情 | 详情 | |
| (XXV) | 58019 | ethyl 5-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]pentanoate | C12H22O4 | 详情 | 详情 |