反応式
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12](F)(F)F)=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[N:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][N:17]=1.[OH:26]S(O)(=O)=O.[OH2:31]>>[C:12]([C:8]1[CH:7]=[C:6]2[C:11]([C:2]([Cl:1])=[CH:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1)([OH:26])=[O:31].[N:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][N:17]=1参加物
実験手順
As shown in Scheme 7, halogenated azaarenes 23, exemplified by 4-chloro-7-trifluoromethylquinoline or cinnoline, are treated with H2SO4 (70-95%) at 180-220° C. for about 16 to 48 hours in a sealed reaction vessel. The solution is cooled, poured into water and neutralized with base to pH ˜3-4. The product is dissolved in aqueous base and precipitated by acidification to yield 7-carboxy-4-chloroquinoline or cinnoline. This material is converted to the alkyl ester, such as methyl (24) or ethyl, by standard methods. 7-Alkyloxycarbonyl-4-chloroquinoline or cinnoline is dissolved in an anhydrous, aprotic solvent (THF or ether). The solution is cooled (−60 to −95° C.) and treated with a reducing agent such as lithium aluminum hydride. The solution is warmed (to approximately −40 to −50° C.) for about 15 to 30 minutes and quenched with a solvent such as ethyl acetate. Standard workup gives the product 7-hydroxymethyl-4-chloroquinoline, or cinnoline (25). Material 25 is treated with 45-50% HBr and heated to about 100-140° C. for about 45 to 90 minutes. After cooling and standard workup, 7-bromomethyl-4-chloroquinoline (or cinnoline) 26 is obtained. Alkylation as described before provides 4-chloroquinoline (or cinnoline) 27 followed by deprotection under the usual acidic conditions gives 4-chloroquinoline (or cinnoline) 28.
後処理
- temperatureThe solution is cooled
- dissolutionThe product is dissolved in aqueous base
- customprecipitated by acidification
出典と根拠
- ORDレコード
- ord-a40e01f9ebd345c1a0206270594928d7
- 出典データセット
- uspto-grants-2009_11
- 特許番号
- US07612075B2
関連ノート
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