Ethyl Acetate → 3-fluoro-6-methoxyquinoline

反応式

[F:1][B-](F)(F)F.[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][C:12]([N+]#N)=[CH:11]2.C(OCC)(=O)C.[OH-].[Na+]>C1(C)C=CC=CC=1>[F:1][C:12]1[CH:13]=[N:14][C:15]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:7][CH3:6])=[CH:17][CH:16]=2

参加物

反応条件

温度: 60 °C

実験手順

A suspension of 1007 g of 6-methoxy-3-quinolinediazonium fluoroborate taken in 9 l of toluene is heated to 60° C. in 85 minutes. A release of gas is observed at 60° C. The reaction medium is then gradually heated further for 90 minutes to 70-72° C. After having been kept at 72° C. for 90 minutes, the medium is then gradually heated again to 85° C. After cooling and stirring overnight, 4 l of ice-cold water are added to the suspension. After having stirred for 15 minutes, 2.5 l of ethyl acetate are added. After having stirred for 45 minutes, the pH is adjusted to pH=7-7.5 by adding 47% sodium hydroxide (250 ml). The medium is stirred for 30 minutes and then separated by settling out for 1 hour. The lower aqueous phase is re-extracted with ethyl acetate. The organic phases are combined together and washed with water. The solution is filtered and then concentrated under reduced pressure so as to give 655 g of crude 3-fluoro-6-methoxyquinoline. The crude product is distilled under reduced pressure. The distillation fractions (bp 103-110° C. under 1 mbar) containing the expected product are combined together. 498.9 g of 3-fluoro-6-methoxyquinoline (76%) are thus obtained in the form of a white solid which melts at 51-53° C.