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

HRID 862160

반응식

HRID 862160 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 7416Nitrobenzene용매

실험 절차

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 (6x500 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.

후처리

  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 (6x500 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

출처 및 근거

ORD 기록
ord-49d7bff2ad6d4d2d8138163562204d15
출처 데이터셋
uspto-grants-1998_02
특허 번호
US05717099

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