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【结 构 式】 
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【分子编号】21231 【品名】ethyl 2-[4-(acetamido)phenyl]acetate 【CA登记号】 |
【 分 子 式 】C12H15NO3 【 分 子 量 】221.25604 【元素组成】C 65.14% H 6.83% N 6.33% O 21.69% |
合成路线1
该中间体在本合成路线中的序号：(IX)The methylation of ethyl 4-nitrophenylacetate (I) with NaH - ICH3 in DMF - toluene to ethyl 2-(4-nitrophenyl)propionate (II), which was reduced with H2 over Pd/C in EtOH - H2O to ethyl 2-(4-aminophenyl)propionate (III) (HCl deriv., m.p. 137-40 C). This product was acetylated with acetic anhydride to ethyl 2-(acetylaminophenyl) propionate (IV), m.p. 88-90 C, which was chlorinated with Cl2 in acetic acid to ethyl 2-(3-chloro-4-acetylaminophenyl)propionate (V), b.p. 155-60 C/0.7 mm; this, in turn, was hydrolyzed with HCl in EtOH to ethyl 2-(3-chloro-4-aminophenyl)propionate hydrochloride (VI), m.p. 164-8 C. The last step being the reaction of the preceding intermediate with cis-1,4-dichloro (or dibromo)-2-butene (A) in DMF and Na2CO3 to ethyl 2-(3-chloro-4-(3-pyrrolinyl)phenyl)propionate (VII), b.p. 128-33 C/0.25 mm; followed by hydrolysis with KOH in EtOH - H2O. The acetylation of ethyl 4-aminophenylacetate (VIII) with acetic anhydride to ethyl 4-acetylaminophenylacetate (IX), m.p. 75-8 C, followed by methylation with ICH3 and Na in liquid NH3 to ethyl 2-(4-acetylaminophenyl)propionate (IV), already obtained.
| 【1】 Carney, R.W.J.; de Stevens, G; Tertiary amino phenyl acetic acids. CH 574926; CH 577968; CH 578523; CH 581103; CH 581104; US 3641040 . |
| 【2】 Castaner, J.; Pirprofen. Drugs Fut 1977, 1, 1, 23. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 32186 | (E)-1,4-dichloro-2-butene | 110-57-6 | C4H6Cl2 | 详情 | 详情 |
| (I) | 33982 | ethyl 2-(4-nitrophenyl)acetate | 5445-26-1 | C10H11NO4 | 详情 | 详情 |
| (II) | 33983 | ethyl 2-(4-nitrophenyl)propanoate | C11H13NO4 | 详情 | 详情 | |
| (III) | 33984 | ethyl 2-(4-aminophenyl)propanoate | C11H15NO2 | 详情 | 详情 | |
| (IV) | 33985 | ethyl 2-[4-(acetamido)phenyl]propanoate | C13H17NO3 | 详情 | 详情 | |
| (V) | 33986 | ethyl 2-[4-(acetamido)-3-chlorophenyl]propanoate | C13H16ClNO3 | 详情 | 详情 | |
| (VI) | 33987 | ethyl 2-(4-amino-3-chlorophenyl)propanoate | C11H14ClNO2 | 详情 | 详情 | |
| (VII) | 33988 | ethyl 2-[3-chloro-4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl]propanoate | C15H18ClNO2 | 详情 | 详情 | |
| (VIII) | 21230 | ethyl 2-(4-aminophenyl)acetate | 5438-70-0 | C10H13NO2 | 详情 | 详情 |
| (IX) | 21231 | ethyl 2-[4-(acetamido)phenyl]acetate | C12H15NO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)The esterification of 4-aminophenylacetic acid (I) with ethanol - HCl in the usual way gives the ethyl ester (II), which is acylated with acetic anhydride in ethyl acetate yielding ethyl 4-acetaminophenylacetate (III). Finally, this compound is hydrolyzed with aqueous NaOH.
| 【1】 Sato, S.; Tsurufuji, M.; Enomoto, H.; Sugiyama, M.; Shibata, Y.; Morita, I.; Munakata, H.; Kobayashi, M.; Wagatsuma, K. (Mitsubishi Chem. Inds. Co.; Ltd.); Immunomodulating agents. DE 3317107; US 4720506 . |
| 【2】 Prous, J.; Castaner, J.; MS-932. Drugs Fut 1989, 14, 8, 759. |