(2,3-Difluorophenyl)boronic acid → HCID 59226502, compound

HRID 1523476Notes

Reaction equation

HRID 1523476 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][C:3]=1[F:11].[F:12][C:13]1[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=1B(O)O>COCCOC.C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C.[OH-].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:12][C:13]1[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=1[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][C:3]=1[F:11]

Participants

8

Reactant 2

HCID 2734333(2,3-Difluorophenyl)boronic acidHCID 534011946-Bromo-5-fluoropicolinic Acid

Product 1

HCID 59226502HCID 59226502, compound

Reagents, catalysts & solvents 5

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 6-bromo-5-fluoropicolinic acid (1.0 equiv.) in DME and 2M Na2CO3 (3:1, 0.25 M) was added 2,3-difluorophenylboronic acid (1.3 equiv.) and Pd(dppf)Cl2-DCM (0.05 equiv.) in a microwave vial. The vial was heated in the microwave at 120° C. for 30 minutes. The mixture was diluted with ethyl acetate and 1N NaOH was added. The organic phase was separated and extracted three more times with 1N NaOH and once with 6N NaOH. The combined aqueous phases were filtered and acidified to pH 1 by the addition of concentrated HCl and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated to give 6-(2,3-difluorophenyl)-5-fluoropicolinic acid in 78%. LC/MS=254.1 (M+H), Rt=0.75 min.

Workup

  1. additionwas added
  2. customThe organic phase was separated
  3. extractionextracted three more times with 1N NaOH
  4. filtrationThe combined aqueous phases were filtered
  5. additionacidified to pH 1 by the addition of concentrated HCl
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-dd8cf8d2db144611a16e96f3228cdea7
Source dataset
uspto-grants-2015_07
Patent number
US09079889B2

Reaction notes

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