|
【结 构 式】 
|
【分子编号】44399 【品名】2-bromo-6-methoxynaphthalene; 6-bromo-2-naphthyl methyl ether 【CA登记号】5111-65-9 |
【 分 子 式 】C11H9BrO 【 分 子 量 】237.09586 【元素组成】C 55.72% H 3.83% Br 33.7% O 6.75% |
合成路线1
该中间体在本合成路线中的序号：(IV)The bromination of beta-naphthol (I) gives the 1,6-dibromo-beta-naphthol (II), which is partially debrominated with Sn and BrH, yielding 1-bromo-beta-naphthol (III). The methylation of (III) with methanol/sulfuric acid affords the corresponding methyl ether (IV), which is treated with Mg and DMF to provide 6-methoxynaphthalene-2-carbaldehyde (V). The condensation of (V) with ethyl acetoacetate (VI) gives the expected adduct (VII), which is reduced with H2 over Pd/C to provide 2-acetyl-3-(6-methoxy-2-naphthyl)propionic acid ethyl ester (VIII). Finally, this compound is decarboxylated with aqueous HCl.
| 【1】 Zhang, G.; et al.; A study on the synthesis of a new anti-inflammatory agent - nabumetone. J Shenyang Coll Pharm 1988, 5, 4, 259. |
| 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) | 44396 | 2-naphthol | 135-19-3 | C10H8O | 详情 | 详情 |
| (II) | 44397 | 1,6-dibromo-2-naphthol | 16239-18-2 | C10H6Br2O | 详情 | 详情 |
| (III) | 44398 | 6-bromo-2-naphthol | 15231-91-1 | C10H7BrO | 详情 | 详情 |
| (IV) | 44399 | 2-bromo-6-methoxynaphthalene; 6-bromo-2-naphthyl methyl ether | 5111-65-9 | C11H9BrO | 详情 | 详情 |
| (V) | 29956 | 6-Methoxy-2-naphthaldehyde | 3453-33-6 | C12H10O2 | 详情 | 详情 |
| (VI) | 11819 | ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate | 141-97-9 | C6H10O3 | 详情 | 详情 |
| (VII) | 29957 | ethyl (Z)-2-acetyl-3-(6-methoxy-2-naphthyl)-2-propenoate | C18H18O4 | 详情 | 详情 | |
| (VIII) | 29958 | ethyl 2-[(6-methoxy-2-naphthyl)methyl]-3-oxobutanoate | C18H20O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The condensation of 2-bromo-6-methoxynaphthalene (I) with 3-buten-2-one (II) by means of PdCl2, PPh3 and K2CO3 in DMF at 132 C gives 4-(6-methoxy-2-naphthyl)-3-buten-2-one (III), which is then hydrogenated with H2 over Pd/C in DMF. The same condensation can be performed with PdCl2 , PPh3 and NaHCO3 in 1-methyl-2-pyrrolidone at 130 C. The reaction of 4-hydroxy-2-butanone (IV) with acetic anhydride or acetyl chloride gives 4-acetyl-2-butanone (V), which is condensed with 2-bromo-6-methoxynaphthalene (I) by means of PdCl2, PPh3 and K2CO3 in DMF at 132 C to yield the previously reported 4-(6-methoxy-2-naphthyl)-3-buten-2-one (III).
| 【1】 Aslam, M.; et al.; Convenient synthesis of nabumetone. Synthesis 1989, 869. |
| 【2】 Fritch, J.R.; Rios, D.E.; Smith, J.C.; Aslam, M. (Celanese AG); Use of 4-substd. 2-butanones to prepare nabumetone. WO 9640608 . |
| 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) | 44399 | 2-bromo-6-methoxynaphthalene; 6-bromo-2-naphthyl methyl ether | 5111-65-9 | C11H9BrO | 详情 | 详情 |
| (II) | 30324 | 3-buten-2-one; methyl vinyl ketone | 78-94-4 | C4H6O | 详情 | 详情 |
| (III) | 32194 | (E)-4-(6-methoxy-2-naphthyl)-3-buten-2-one | C15H14O2 | 详情 | 详情 | |
| (IV) | 46053 | 4-hydroxy-2-butanone | C4H8O2 | 详情 | 详情 | |
| (V) | 46054 | 3-oxobutyl acetate | C6H10O3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)By condensation of 2-bromo-6-methoxynaphthalene (I) with 3-buten-2-ol (VI) catalyzed by Pd(OAc)2 or PdCl2, along with PPh3 and NaHCO3 in 1-methyl-2-pyrrolidone at 140 C. The reaction of 2-bromo-6-methoxynaphthalene (I) with Mg in THF gives the expected Grignard reagent (VII), which is then condensed with 3-buten-2-one (II) by means of ZnCl2-amine complex in the same solvent.
| 【1】 Aslam, M.; et al.; Convenient synthesis of nabumetone. Synthesis 1989, 869. |
| 【2】 Wang, S.-M.; Chen, Z.-X.; Novel synthesis of nabumetone. Chin J Pharm 1989, 20, 4, 146. |
| 【3】 Davenport, K.G.; Aslam, M. (Celanese AG); Method of preparation of nabumetone. EP 0376516 . |