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【结 构 式】 
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【分子编号】42985 【品名】ethyl 2-(4-bromobenzyl)acrylate 【CA登记号】 |
【 分 子 式 】C12H13BrO2 【 分 子 量 】269.13802 【元素组成】C 53.55% H 4.87% Br 29.69% O 11.89% |
合成路线1
该中间体在本合成路线中的序号：(IV)Treatment of triethyl phosphoacetate (I) with NaH and 4-bromobenzyl bromide (II) in DMF provides the 2-substituted triethyl phosphoacetate (III), which then undergoes reaction with formaldehyde and K2CO3 to afford acrylate derivative (IV). Michael condensation of (IV) with phosphinic acid (V) in N,O-bistrimethylsilylacetamide (BSA) yields intermediate (VI), which then undergoes Suzuki condensation in toluene with phenylboronic acid (VII) and NaHCO3 in MeOH catalyzed by Pd(PPh3)4 to give (VIII). Hydrolysis of ethyl ester (VIII) by means of NaOH in EtOH furnishes carboxylic acid (IX), which is then coupled to L-alanine (X) by means of BOP and DIEA or Et3N in DMF to yield methyl ester (XI). Compound (XI) is then hydrolyzed by treatment with NaOH or LiOH in EtOH and, finally, the Z-protecting group is removed with BBr3 in dichloromethane.
| 【1】 Chen, H.; Noble, F.; Coric, P.; Fournie-Zaluski, M.-C.; Roques, B.P.; Aminophosphinic inhibitors as transition state analogues of enkephalin-degrading enzymes: A class of central analgesics. Proceedings of the National Academy of Sciences of the United States of America 1998, 95, 20, 12028. |
| 【2】 Noble, F.; Morthé, A.; Chen, H.; et al.; Phosphinic derivatives as new dual enkephalin-degrading enzyme inhibitors: Synthesis, biological properties, and antinociceptive activities. J Med Chem 2000, 43, 7, 1398. |
| 【3】 Fournie-Zaluski, M.-C.; Chen, H.; Roques, B.P. (INSERM (Institut National de la Sante et de la Recherche Medicale)); Novel (alpha-aminophosphino) peptide derivs., method for making same and therapeutic applications thereof. EP 1009750; WO 9818803 . |
| 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) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (II) | 16109 | 1-bromo-4-(bromomethyl)benzene; 4-Bromobenzyl bromide | 589-15-1 | C7H6Br2 | 详情 | 详情 |
| (III) | 42984 | ethyl 3-(4-bromophenyl)-2-(diethoxyphosphoryl)propanoate | C15H22BrO5P | 详情 | 详情 | |
| (IV) | 42985 | ethyl 2-(4-bromobenzyl)acrylate | C12H13BrO2 | 详情 | 详情 | |
| (V) | 42986 | 1-[[(benzyloxy)carbonyl]amino]ethylphosphinic acid | C10H14NO4P | 详情 | 详情 | |
| (VI) | 42987 | 1-[[(benzyloxy)carbonyl]amino]ethyl[2-(4-bromobenzyl)-3-ethoxy-3-oxopropyl]phosphinic acid | C22H27BrNO6P | 详情 | 详情 | |
| (VII) | 16593 | Phenylboronic acid；Benzeneboronic acid;Phenylboron dihydroxide | 98-80-6 | C6H7BO2 | 详情 | 详情 |
| (VIII) | 42988 | 1-[[(benzyloxy)carbonyl]amino]ethyl[2-([1,1'-biphenyl]-4-ylmethyl)-3-ethoxy-3-oxopropyl]phosphinic acid; 4-(2-[[(1-[[(benzyloxy)carbonyl]amino]ethyl)(hydroxy)phosphoryl]methyl]-3-ethoxy-3-oxopropyl)-1,1'-biphenyl | C28H32NO6P | 详情 | 详情 | |
| (IX) | 42989 | 3-[(1-[[(benzyloxy)carbonyl]amino]ethyl)(hydroxy)phosphoryl]-2-([1,1'-biphenyl]-4-ylmethyl)propionic acid | C26H28NO6P | 详情 | 详情 | |
| (X) | 20694 | methyl (2S)-2-aminopropanoate | C4H9NO2 | 详情 | 详情 | |
| (XI) | 42990 | 1-[[(benzyloxy)carbonyl]amino]ethyl(2-([1,1'-biphenyl]-4-ylmethyl)-3-[[(1S)-2-methoxy-1-methyl-2-oxoethyl]amino]-3-oxopropyl)phosphinic acid; 4-(2-[[(1-[[(benzyloxy)carbonyl]amino]ethyl)(hydroxy)phosphoryl]methyl]-3-[[(1S)-2-methoxy-1-methyl-2-oxoethyl]amino]-3-oxopropyl)-1,1'-biphenyl | C30H35N2O7P | 详情 | 详情 |