|
【结 构 式】 
|
【分子编号】35205 【品名】3,5-di(tert-butyl)-4-hydroxybenzamide 【CA登记号】 |
【 分 子 式 】C15H23NO2 【 分 子 量 】249.35316 【元素组成】C 72.25% H 9.3% N 5.62% O 12.83% |
合成路线1
该中间体在本合成路线中的序号：(III)3,5-Di-tert-butyl-4-hydroxybenzoic acid (I) was converted to amide (III) via activation as the acyl imidazole (II) followed by treatment with aqueous ammonia. Subsequent condensation of (III) with ethyl 4-chloroacetoacetate (IV) produced oxazole (V). Basic hydrolysis of the ethyl ester of (V) yielded carboxylic acid (VI), which was reduced to alcohol (VII) with borane in THF. Treatment of (VII) with methanesulfonyl chloride and triethylamine generated mesylate (VIII). This was coupled with 4-hydroxybenzaldehyde (IX), yielding ether (X). Finally, reductive condensation of (X) with ethyl methylamine in the presence of NaBH3CN furnished the corresponding tertiary amine.
| 【1】 Heinz, L.J.; Panetta, J.A.; Phillips, M.L.; Shadle, J.K. (Eli Lilly and Company); Novel cpds. useful as neuro-protective agents. EP 0971709; WO 9815274 . |
| 【2】 Shannon, H.E.; Panetta, J.A. (Eli Lilly and Company); Method for treating pain. WO 9909980 . |
| 【3】 Shannon, H.E.; Panetta, J.A. (Eli Lilly and Company); Method for treating neuropathic pain. WO 9909979 . |
| 【4】 Heinz, L.J.; Panetta, J.A.; Phillips, M.L.; Rieck, J.A.; Rizzo, J.R.; Shadle, J.K.; Varie, D.L.; Anderson, B.A. (Eli Lilly and Company); Oxazoles, thiazoles, oxazolines, oxadiazoles and benzoxazoles useful as neuro-protective agents. EP 0908454; WO 9918091 . |
| 【5】 Panetta, J.A.; Shannon, H.E. (Eli Lilly and Company); Method for treating pain. WO 9909829 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 40588 | N-methyl-1-ethanamine; N-ethyl-N-methylamine | 624-78-2 | C3H9N | 详情 | 详情 | |
| (I) | 19980 | 3,5-di(tert-butyl)-4-hydroxybenzoic acid | 1421-49-4 | C15H22O3 | 详情 | 详情 |
| (II) | 35204 | [3,5-di(tert-butyl)-4-hydroxyphenyl](1H-imidazol-1-yl)methanone | C18H24N2O2 | 详情 | 详情 | |
| (III) | 35205 | 3,5-di(tert-butyl)-4-hydroxybenzamide | C15H23NO2 | 详情 | 详情 | |
| (IV) | 23541 | ethyl 4-chloro-3-oxobutanoate；Ethyl 4-chloro-3-oxobutanoate；Ethyl 4-chloroacetoacetate | 638-07-3 | C6H9ClO3 | 详情 | 详情 |
| (V) | 35206 | ethyl 2-[2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazol-4-yl]acetate | C21H29NO4 | 详情 | 详情 | |
| (VI) | 35207 | 2-[2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazol-4-yl]acetic acid | C19H25NO4 | 详情 | 详情 | |
| (VII) | 35208 | 2,6-di(tert-butyl)-4-[4-(2-hydroxyethyl)-1,3-oxazol-2-yl]phenol | C19H27NO3 | 详情 | 详情 | |
| (VIII) | 35209 | 2-[2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazol-4-yl]ethyl methanesulfonate | C20H29NO5S | 详情 | 详情 | |
| (IX) | 13433 | 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde | 123-08-0 | C7H6O2 | 详情 | 详情 |
| (X) | 35210 | 4-(2-[2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazol-4-yl]ethoxy)benzaldehyde | C26H31NO4 | 详情 | 详情 |