Acetic Acid → 2-(4-Bromophenoxy)-5-methoxynicotinic acid

HRID 1409499Notes

Reaction equation

HRID 1409499 reaction equation
[H-].[Na+].CN(C=O)C.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1.F[C:17]1[N:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:18]=1[C:19]([OH:21])=[O:20].C(O)(=O)C.Cl>>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:17]2[N:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:18]=2[C:19]([OH:21])=[O:20])=[CH:11][CH:10]=1

Participants

7

Reactant 6

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 78084-BromophenolHCID 24758Sodium hydrideHCID 667280732-Fluoro-5-methoxynicotinic acid

Product 1

HCID 667281662-(4-Bromophenoxy)-5-methoxynicotinic acid

Conditions

Temperature
0 °C

Procedure

To a slurry of sodium hydride (60% dispersion) (21.74 g, 543 mmol) in DMF (351 mL, 175 mmol) at 0° C. was added 4-bromophenol (60.7 g, 351 mmol) over the course of 5 minutes. Stirred at 0° C. for two minutes then removed from the ice bath and stirred for an additional 5 minutes at room temperature. Added 2-fluoro-5-methoxynicotinic acid (30 g, 175 mmol) portionwise over 10 minutes and heated the resulting slurry at 140° C. After cooling to room temperature the mixture was then poured onto 1 kg of ice and was quenched with acetic acid (50.2 mL, 877 mmol) and then 75 mL of 6 N HCl. Stirred vigorously for 1 hour, leading to the formation of a red slurry containing a very fine white precipitate. Filtered the slurry to provide 2-(4-bromophenoxy)-5-methoxynicotinic acid.

Workup

  1. customthen removed from the ice bath
  2. stirringstirred for an additional 5 minutes at room temperature
  3. temperatureheated the resulting slurry at 140° C
  4. temperatureAfter cooling to room temperature the mixture
  5. stirringStirred vigorously for 1 hour
  6. additioncontaining a very fine white precipitate
  7. filtrationFiltered the slurry

Sources & evidence

ORD record
ord-66eda594548140f7bc3a9f25e46f1576
Source dataset
uspto-grants-2014_12
Patent number
US08921363B2

Reaction notes

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