【结 构 式】 |
【分子编号】38039 【品名】2-[(1S)-1-(hydroxymethyl)-2-propenyl]-1H-isoindole-1,3(2H)-dione 【CA登记号】 |
【 分 子 式 】C12H11NO3 【 分 子 量 】217.22428 【元素组成】C 66.35% H 5.1% N 6.45% O 22.1% |
合成路线1
该中间体在本合成路线中的序号:(III)The enantiocontrolled addition of phthalimide (I) to 1,3-butadiene monoepoxide (II) with a chiral palladium catalyst and Na2CO3 in dichloromethane gives N-(2-hydroxy-1(S)-vinylethyl)phthalimide (III), which is treated with triflic anhydride and TEA in dichloromethane to yield the triflate (IV). The condensation of (IV) with dimethyl malonate (V) by means of NaH in THF affords the alkylated malonate (VI), which is finally decarboxylated and deprotected by a treatment with aqueous refluxing HCl. Note that the synthesis of the biologically active (S)-enantiomer simply requires a change in the chirality of the Pd catalyst used in the first step of the synthesis.
【1】 Trost, B.M.; et al.; Dynamic kinetic asymetric transformation of diene monoepoxides: A practical asymmetric synthesis of vinylglycinol, vigabatrin, and ethambutol. J Am Chem Soc 2000, 122, 25, 5968. |
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) | 12376 | Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione | 85-41-6 | C8H5NO2 | 详情 | 详情 |
(II) | 32805 | 2-vinyloxirane | 930-22-3 | C4H6O | 详情 | 详情 |
(III) | 38039 | 2-[(1S)-1-(hydroxymethyl)-2-propenyl]-1H-isoindole-1,3(2H)-dione | C12H11NO3 | 详情 | 详情 | |
(IV) | 38040 | (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-butenyl trifluoromethanesulfonate | C13H10F3NO5S | 详情 | 详情 | |
(V) | 19373 | dimethyl malonate;Methyl malonate;Propanedioic acid dimethyl ester | 108-59-8 | C5H8O4 | 详情 | 详情 |
(VI) | 38041 | dimethyl 2-[(2R)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-butenyl]malonate | C17H17NO6 | 详情 | 详情 |