|
【结 构 式】 
|
【分子编号】59559 【品名】Dimethyl acetonylphosphonate; Acetylmethylphosphonic acid dimethyl ester; Dimethyl (2-oxopropyl)phosphonate 【CA登记号】4202-14-6 |
【 分 子 式 】C5H11O4P 【 分 子 量 】166.113702 【元素组成】C 36.15% H 6.67% O 38.53% P 18.65% |
合成路线1
该中间体在本合成路线中的序号：(V)The required phosphonate reagent (IV) was prepared by two alternative methods. Bromination of benzylacetone (I) in cold methanol afforded 1-bromo-4-phenyl-2-butanone (II). Subsequent displacement of the bromide ion of (II) with NaI in acetone led to the iodo ketone (III). The desired phosphonate (IV) was then obtained by the Arbuzov reaction of (III) with trimethyl phosphite. Alternatively, alkylation of the dianion of dimethyl 2-oxopropyl phosphonate (V) with benzyl bromide led to phosphonate (IV).
| 【1】 Gutman, A.; Nisnevich, G.; Etinger, M.; Zaltzman, I.; Judovich, L.; Pertsikov, B.; A new process for the preparation of latanoprost. WO 0155101 . |
| 【2】 Resul, B.; et al.; Phenyl-substituted prostaglandins: Potent and selective antiglaucoma agents. J Med Chem 1993, 36, 2, 243. |
| 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) | 32061 | 4-phenyl-2-butanone | 2550-26-7 | C10H12O | 详情 | 详情 |
| (II) | 29211 | 1-bromo-4-phenyl-2-butanone | C10H11BrO | 详情 | 详情 | |
| (III) | 59557 | 1-iodo-4-phenyl-2-butanone | C10H11IO | 详情 | 详情 | |
| (IV) | 59558 | dimethyl 2-oxo-4-phenylbutylphosphonate | C12H17O4P | 详情 | 详情 | |
| (V) | 59559 | Dimethyl acetonylphosphonate; Acetylmethylphosphonic acid dimethyl ester; Dimethyl (2-oxopropyl)phosphonate | 4202-14-6 | C5H11O4P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)The butenoic ester intermediate (VIII) has been obtained as follows: The condensation of the known aldehyde (I) with phosphonate (II) by means of KHMDS in THF gives the unsaturated ester (III), which is selectively hydrolyzed at its benzoate group by means of K2CO3 in methanol to yield the ethanol derivative (IV). The oxidation of (IV) by means of DMP affords the acetaldehyde (V), which is condensed with the phosphorane (VI) by means of DBU and LiCl in acetonitrile to provide the methyl ketone (VII) (1). Finally, this compound is methylated by means of Me2Zn and Ni(acac)2 in ethyl ether to give the target butenoic ester intermediate (VIII)
| 【1】 Paterson, I.; et al.; Total synthesis of the microtubule-stabilizing agent (-)-laulimalide. Org Lett 2001, 3, 20, 3149. |
| 【2】 Paterson, I.; et al.; Synthesis of the macrocyclic core of laulimalide. Org Lett 2001, 3, 2, 213. |
| 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) | 61164 | 2-[(2S,6R)-6-(2-oxoethyl)-3,6-dihydro-2H-pyran-2-yl]ethyl benzoate | C16H18O4 | 详情 | 详情 | |
| (II) | 41856 | methyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetate | 88738-78-7 | C7H9F6O5P | 详情 | 详情 |
| (III) | 61165 | 2-{(2S,6R)-6-[(Z)-4-methoxy-4-oxo-2-butenyl]-3,6-dihydro-2H-pyran-2-yl}ethyl benzoate | C19H22O5 | 详情 | 详情 | |
| (IV) | 61166 | methyl (Z)-4-[(2R,6S)-6-(2-hydroxyethyl)-5,6-dihydro-2H-pyran-2-yl]-2-butenoate | C12H18O4 | 详情 | 详情 | |
| (V) | 59559 | Dimethyl acetonylphosphonate; Acetylmethylphosphonic acid dimethyl ester; Dimethyl (2-oxopropyl)phosphonate | 4202-14-6 | C5H11O4P | 详情 | 详情 |
| (VI) | 61167 | methyl (Z)-4-[(2R,6S)-6-(2-oxoethyl)-5,6-dihydro-2H-pyran-2-yl]-2-butenoate | C12H16O4 | 详情 | 详情 | |
| (VII) | 61168 | methyl (Z)-4-{(2R,6S)-6-[(E)-4-oxo-2-pentenyl]-5,6-dihydro-2H-pyran-2-yl}-2-butenoate | C15H20O4 | 详情 | 详情 | |
| (VIII) | 61169 | methyl (Z)-4-{(2R,6R)-6-[(2R)-2-methyl-4-oxopentyl]-5,6-dihydro-2H-pyran-2-yl}-2-butenoate | C16H24O4 | 详情 | 详情 |