1,4-Difluorobenzene → 3-(2,5-Difluorobenzoyl)isonicotinic acid

HRID 52404

反応式

HRID 52404 の反応式
[N:1]1[CH:6]=[CH:5][C:4]2[C:7]([O:9][C:10](=[O:11])[C:3]=2[CH:2]=1)=[O:8].[Al+3].[Cl-].[Cl-].[Cl-].[F:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1.FC1C=CC(F)=CC=1C(C1C(C(O)=O)=CN=CC=1)=O>[N+](C1C=CC=CC=1)([O-])=O>[F:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[C:10]([C:3]1[CH:2]=[N:1][CH:6]=[CH:5][C:4]=1[C:7]([OH:9])=[O:8])=[O:11]

参加物

6

反応物 4

HCID 108921,4-DifluorobenzeneHCID 2783981H,3H-furo(3,4-c)pyridine-1,3-dioneHCID 6451240Aluminum(III) ChlorideHCID 104679084-(2,5-Difluorobenzoyl)nicotinic acid

生成物 1

HCID 100156123-(2,5-Difluorobenzoyl)isonicotinic acid収率 84%

試薬・触媒・溶媒 1

HCID 7416Nitrobenzene溶媒

実験手順

3,4-Pyridine dicarboxylic acid anhydride (95.7 g, 0.67 mol) and AlCl3 (367.3 g, 2.67 mol) were simultaneously, but separately, added in five portions (one every 15') to boiling 1,4-difluorobenzene (650 mL, 90° C.). After about 1 hour from the last addition, the majority of the 1,4-difluorobenzene was removed by distillation at normal pressure until a thick mass was obtained. The temperature was lowered to 80° C. and nitrobenzene (150 mL) was added in order to dissolve the residual mass. While still hot, the resulting solution was cautiously quenched into ice-cooled and stirred water (1000 g of ice and 530 g of demineralized water) (i.e., slowly drop the solution into the ice water). Then concentrated HCl (37%, 160 mL) was added to the poured mixture at 0°-5° C. and stirring was continued for about 3 hours. A greasy beige precipitate (about 150 g wet) was collected by filtration while the aqueous layer was separated from nitrobenzene and extracted with AcOEt (6×500 mL). Nitrobenzene layer was diluted with petroleum ether (400 mL) and the resulting little amount of precipitate was collected by filtration (about 2 g). Combined extracts were concentrated under vacuum, and the residual crude solid (about 45 g), together with the previously collected precipitates, was suspended into a mixture of AcOEt/petroleum ether (1/1) (600 mL). After about 2 hours at room temperature the suspension was filtered and dried in vacuum to give the mixture of 4-(2',5'-difluorobenzoyl)nicotinic acid and 3-(2',5'-difluorobenzoyl)isonicotinic acid (147.3 g, 84% yield) as a pale beige solid.

後処理

  1. additionseparately, added in five portions (one every 15')
  2. additionAfter about 1 hour from the last addition
  3. customthe majority of the 1,4-difluorobenzene was removed by distillation at normal pressure until a thick mass
  4. customwas obtained
  5. customwas lowered to 80° C.
  6. dissolutionto dissolve the residual mass
  7. customWhile still hot, the resulting solution was cautiously quenched into ice-
  8. temperaturecooled
  9. additionThen concentrated HCl (37%, 160 mL) was added to the poured mixture at 0°-5° C.
  10. stirringstirring
  11. filtrationA greasy beige precipitate (about 150 g wet) was collected by filtration while the aqueous layer
  12. customwas separated from nitrobenzene
  13. extractionextracted with AcOEt (6×500 mL)
  14. additionNitrobenzene layer was diluted with petroleum ether (400 mL)
  15. filtrationthe resulting little amount of precipitate was collected by filtration (about 2 g)
  16. concentrationCombined extracts were concentrated under vacuum
  17. customthe residual crude solid (about 45 g), together with the previously collected
  18. customprecipitates
  19. additionwas suspended into a mixture of AcOEt/petroleum ether (1/1) (600 mL)
  20. filtrationAfter about 2 hours at room temperature the suspension was filtered
  21. customdried in vacuum
  22. customto give

出典と根拠

ORDレコード
ord-0636c752c7a8408b93a89cbb2c713c9d
出典データセット
uspto-grants-1997_04
特許番号
US05616709

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