Formic Acid → 4-[(6,7-Dimethoxyquinolin-4-yl)oxy]aniline

HRID 331210Notes

Reaction equation

HRID 331210 reaction equation
C([O-])=O.[K+].C(O)=O.O.[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][C:20]=1[O:21][CH3:22])[N:17]=[CH:16][CH:15]=[C:14]2[O:23][C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-])=O)=[CH:26][CH:25]=1>[Pd].O1CCCC1>[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][C:20]=1[O:21][CH3:22])[N:17]=[CH:16][CH:15]=[C:14]2[O:23][C:24]1[CH:25]=[CH:26][C:27]([NH2:30])=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 284Formic AcidHCID 962WaterHCID 2735122Potassium FormateHCID 22132806Quinoline, 6,7-dimethoxy-4-(4-nitrophenoxy)-

Product 1

HCID 115945434-[(6,7-Dimethoxyquinolin-4-yl)oxy]anilineYield 97%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution containing potassium formate (5.0 kg), formic acid (3.0 kg), and water (16.0 kg) was added to a mixture of 6,7-dimethoxy-4-(4-nitro-phenoxy)-quinoline (4.0 kg), 10% palladium on carbon (50% water wet, 0.4 kg) in tetrahydrofuran (40.0 kg) that had been heated to approximately 60° C. The addition was carried out such that the temperature of the reaction mixture remained approximately 60° C. When the reaction was deemed complete as determined using in-process HPLC analysis (<2% starting material remaining, typically 1 5 hours), the reactor contents were filtered. The filtrate was concentrated by vacuum distillation at approximately 35° C. to half of its original volume, which resulted in the precipitation of the product. The product was recovered by filtration, washed with water (12.0 kg), and dried under vacuum at approximately 50° C. to afford the title compound (3.0 kg; 97% AUC).

Workup

  1. additionThe addition
  2. customremained approximately 60° C
  3. filtrationtypically 1 5 hours), the reactor contents were filtered
  4. concentrationThe filtrate was concentrated by vacuum distillation at approximately 35° C. to half of its original volume, which
  5. customresulted in the precipitation of the product
  6. filtrationThe product was recovered by filtration
  7. washwashed with water (12.0 kg)
  8. customdried under vacuum at approximately 50° C.

Sources & evidence

ORD record
ord-8d3c859e5475480285e080d798aade9a
Source dataset
uspto-grants-2014_11
Patent number
US08877776B2

Reaction notes

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