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【结 构 式】 
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【分子编号】33155 【品名】ethyl (2S)-2-amino-3-(4-hydroxyphenyl)propanoate 【CA登记号】949-67-7 |
【 分 子 式 】C11H15NO3 【 分 子 量 】209.24504 【元素组成】C 63.14% H 7.23% N 6.69% O 22.94% |
合成路线1
该中间体在本合成路线中的序号：(II)Etilevodopa has been obtained by several different methods: (i) esterification of 3-hydroxy-L-tyrosine (I) (L-DOPA) with ethanol catalyzed by dry HCl gas; (ii) esterification of 3-hydroxy-L-tyrosine (I) (L-DOPA) by means of SOCl2 in hot ethanol; (iii) enzymatic hydroxylation of L-tyrosine ethyl ester (II) by means of mushroom tyrosinase in a phosphate buffer.
| 【1】 Sorbera, L.A.; Leeson, P.; Castaner, J.; Martin, L.; Etilevodopa. Drugs Fut 2001, 26, 3, 219. |
| 【2】 Ahmed, G.; Vulfson, E.N.; Facile synthesis of L-Dopa esters by the combined use of tyrosinase and alpha-chymotrypsin. Biotechnol Lett 1994, 16, 4, 367. |
| 【3】 Bahar, E.; Lidor, R.; Frenkel, A. (Teva Pharmaceutical Industries Ltd.; Teva Pharmaceuticals USA, Inc.); Process for manufacture of L-DOPA ethyl ester. US 6218566; WO 0027801 . |
| 【4】 Atlas, D.; Veinberg, A.; Melamed, E.; Milman, I. (Teva Pharmaceutical Industries Ltd.; Yissum Research Development Co.); Process for preparing ethyl ester of L-DOPA. EP 0610595; US 5354885 . |
合成路线2
该中间体在本合成路线中的序号：(VIII)The N-protection of 1-aminocyclopentane-1-carboxylic acid (I) with PhCH2-OCOCl and NaOH in tert-butyl methyl ether gives the carbamate (VII), which is condensed with L-tyrosine ethyl ester (VIII) by means isobutyl chloroformate and triethylamine in THF yielding the protected dipeptide (IX). The methylation of (IX) with dimethyl sulfate and K2CO3 in ethyl acetate affords the protected 4-O-methyl dipeptide (X). The deprotection of (X) with HCO2H and Pd/C in ethyl acetate affords the previously reported free dipeptide (V), which is condensed with 2(R)-bromo-3-methylbutyryl chloride (XI) by means of NMM in toluene giving the acylated dipeptide (XII). Finally, this compound is treated with thioacetic acid and K2CO3 in ethyl acetate. The intermediate 2(R)-bromo-3-methylbutyryl chloride (XI) has been obtained by reaction of D-valine (XIII) with NaNO2 and HBr giving the 2(R)-bromo-3-methylbutyric acid (XIV), which is then treated with SOCl2 and DMF to afford the target intermediate (XI).
| 【1】 Johnson, E.P.; et al.; Efficient large scale preparation of neutral endopeptidase/angiotensin-converting enzyme dual inhibitor CGS30440. Org Process Res Dev 1998, 2, 4, 238. |
| 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) | 33149 | 1-aminocyclopentanecarboxylic acid | 52-52-8 | C6H11NO2 | 详情 | 详情 |
| (V) | 33152 | ethyl (2S)-2-[[(1-aminocyclopentyl)carbonyl]amino]-3-(4-methoxyphenyl)propanoate | C18H26N2O4 | 详情 | 详情 | |
| (VII) | 33154 | 1-[[(benzyloxy)carbonyl]amino]cyclopentanecarboxylic acid | C14H17NO4 | 详情 | 详情 | |
| (VIII) | 33155 | ethyl (2S)-2-amino-3-(4-hydroxyphenyl)propanoate | 949-67-7 | C11H15NO3 | 详情 | 详情 |
| (IX) | 33156 | ethyl (2S)-2-[[(1-[[(benzyloxy)carbonyl]amino]cyclopentyl)carbonyl]amino]-3-(4-hydroxyphenyl)propanoate | C25H30N2O6 | 详情 | 详情 | |
| (X) | 33157 | ethyl (2S)-2-[[(1-[[(benzyloxy)carbonyl]amino]cyclopentyl)carbonyl]amino]-3-(4-methoxyphenyl)propanoate | C26H32N2O6 | 详情 | 详情 | |
| (XI) | 33159 | (2R)-2-bromo-3-methylbutanoyl chloride | C5H8BrClO | 详情 | 详情 | |
| (XII) | 33160 | ethyl (2S)-2-[[(1-[[(2R)-2-bromo-3-methylbutanoyl]amino]cyclopentyl)carbonyl]amino]-3-(4-methoxyphenyl)propanoate | C23H33BrN2O5 | 详情 | 详情 | |
| (XIII) | 21056 | (R)-(-)-Valine; D-Valine; (R)-alpha-Aminoisovaleric acid | 640-68-6 | C5H11NO2 | 详情 | 详情 |
| (XIV) | 33158 | (2R)-2-bromo-3-methylbutyric acid | 565-74-2 | C5H9BrO2 | 详情 | 详情 |