【结 构 式】 |
【分子编号】49412 【品名】3-bromopropylphosphonic dichloride 【CA登记号】 |
【 分 子 式 】C3H6BrCl2OP 【 分 子 量 】239.863202 【元素组成】C 15.02% H 2.52% Br 33.31% Cl 29.56% O 6.67% P 12.91% |
合成路线1
该中间体在本合成路线中的序号:(V)The reaction of 1,3-dibromopropane (I) with triethyl phosphite (II) at 160 C gives triethyl 3-bromopropylphosphonate (III), which is treated with Tms-Br and water to yield the corresponding phosphonic acid (IV). The reaction of (IV) with PCl3 in refluxing chloroform affords the acyl chloride (V), which is treated with 4-methoxyphenol (VI) and pyridine to provide the expected 4-methoxyphenyl diester (VII). The reaction of (VII) with N,O-bis(tert-butoxycarbonyl)hydroxylamine (VIII) by means of NaH in DMF gives the fully protected hydroxyamino derivative (IX), which by treatment with TFA in dichloromethane yields 3-(hydroxyamino)propylphosphonic acid 4-methoxyphenyl diester (X). Finally, this compound is acylated with Ac-Cl and TEA in ethyl ether to afford the target N-acetylhydroxyamino compound.
【1】 Reichenberg, A.; et al.; Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activity. Bioorg Med Chem Lett 2001, 11, 6, 833. |
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) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
(II) | 15487 | triethyl phosphite | 122-52-1 | C6H15O3P | 详情 | 详情 |
(III) | 39080 | diethyl 3-bromopropylphosphonate | C7H16BrO3P | 详情 | 详情 | |
(IV) | 39105 | 3-bromopropylphosphonic acid | 1190-09-6 | C3H8BrO3P | 详情 | 详情 |
(V) | 49412 | 3-bromopropylphosphonic dichloride | C3H6BrCl2OP | 详情 | 详情 | |
(VI) | 32744 | 4-methoxyphenol | 150-76-5 | C7H8O2 | 详情 | 详情 |
(VII) | 49413 | bis(4-methoxyphenyl) 3-bromopropylphosphonate | C17H20BrO5P | 详情 | 详情 | |
(VIII) | 34722 | 2-[([[(tert-butoxycarbonyl)amino]oxy]carbonyl)oxy]-2-methylpropane | C10H19NO5 | 详情 | 详情 | |
(IX) | 49414 | 5-(tert-butoxycarbonyl)-1,1-bis(4-methoxyphenoxy)-9,9-dimethyl-1,7-dioxo-6,8-dioxa-5-aza-1lambda(5)-phosphadecane | C27H38NO10P | 详情 | 详情 | |
(X) | 49415 | bis(4-methoxyphenyl) 3-(hydroxyamino)propylphosphonate | C17H22NO6P | 详情 | 详情 |