|
【结 构 式】 
|
【分子编号】63908 【品名】dipropyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate 【CA登记号】 |
【 分 子 式 】C11H20NO3PS 【 分 子 量 】277.324502 【元素组成】C 47.64% H 7.27% N 5.05% O 17.31% P 11.17% S 11.56% |
合成路线1
该中间体在本合成路线中的序号：(X)The intermediate phosphonate (X) has been obtained as follows. The cyclization of thioacetamide (IV) with ethyl 3-bromopiruvate (V) in ethanol gives 2-methylthiazole-4-carboxylic acid ethyl ester (VI), which is reduced by means of LiAlH4 in ethyl ether to yield the carbinol (VII). The bromination of (VII) with CBr4 and PPh3 in CCl4 affords the 4-bromomethyl-2-methylthiazole (VIII), which is finally condensed with triethyl phosphite (IX) to provide the target phosphonate intermediate (X). Alternatively, the cyclization of thioacetamide (IV) with 1,3-dichloroacetone (XI) gives 4-(chloromethyl)-2-methylthiazole (XII), which is condensed with triethyl phosphite (IX) to also provide the target phosphonate intermediate (X).
| 【1】 Jung, J.-K.; Kache, R.; Vines, K.K.; Zheng, Y.-S.; Avery, M.A.; Total synthesis of epothilones B and D amenable to large-scale preparation. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 121. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 19170 | ethanethioamide | 62-55-5 | C2H5NS | 详情 | 详情 |
| (V) | 63904 | propyl 3-bromo-2-oxopropanoate | C6H9BrO3 | 详情 | 详情 | |
| (VI) | 63905 | propyl 2-methyl-1,3-thiazole-4-carboxylate | C8H11NO2S | 详情 | 详情 | |
| (VII) | 63906 | (2-methyl-1,3-thiazol-4-yl)methanol | C5H7NOS | 详情 | 详情 | |
| (VIII) | 63909 | 4-(bromomethyl)-2-methyl-1,3-thiazole | C5H6BrNS | 详情 | 详情 | |
| (IX) | 15487 | triethyl phosphite | 122-52-1 | C6H15O3P | 详情 | 详情 |
| (X) | 63908 | dipropyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate | C11H20NO3PS | 详情 | 详情 | |
| (XI) | 63907 | 1,3-dichloroacetone | C3H4Cl2O | 详情 | 详情 | |
| (XII) | 40819 | 4-(chloromethyl)-2-methyl-1,3-thiazole | C5H6ClNS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)The intermediate phosphonate (X) has been obtained as follows. The cyclization of thioacetamide (IV) with ethyl 3-bromopiruvate (V) in ethanol gives 2-methylthiazole-4-carboxylic acid ethyl ester (VI), which is reduced by means of LiAlH4 in ethyl ether to yield the carbinol (VII). The bromination of (VII) with CBr4 and PPh3 in CCl4 affords the 4-bromomethyl-2-methylthiazole (VIII), which is finally condensed with triethyl phosphite (IX) to provide the target phosphonate intermediate (X). Alternatively, the cyclization of thioacetamide (IV) with 1,3-dichloroacetone (XI) gives 4-(chloromethyl)-2-methylthiazole (XII), which is condensed with triethyl phosphite (IX) to also provide the target phosphonate intermediate (X).
| 【1】 Jung, J.-K.; Kache, R.; Vines, K.K.; Zheng, Y.-S.; Avery, M.A.; Total synthesis of epothilones B and D amenable to large-scale preparation. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 121. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 19170 | ethanethioamide | 62-55-5 | C2H5NS | 详情 | 详情 |
| (V) | 63904 | propyl 3-bromo-2-oxopropanoate | C6H9BrO3 | 详情 | 详情 | |
| (VI) | 63905 | propyl 2-methyl-1,3-thiazole-4-carboxylate | C8H11NO2S | 详情 | 详情 | |
| (VII) | 63906 | (2-methyl-1,3-thiazol-4-yl)methanol | C5H7NOS | 详情 | 详情 | |
| (VIII) | 63909 | 4-(bromomethyl)-2-methyl-1,3-thiazole | C5H6BrNS | 详情 | 详情 | |
| (IX) | 15487 | triethyl phosphite | 122-52-1 | C6H15O3P | 详情 | 详情 |
| (X) | 63908 | dipropyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate | C11H20NO3PS | 详情 | 详情 | |
| (XI) | 63907 | 1,3-dichloroacetone | C3H4Cl2O | 详情 | 详情 | |
| (XII) | 40819 | 4-(chloromethyl)-2-methyl-1,3-thiazole | C5H6ClNS | 详情 | 详情 |