Cesium fluoride → Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoropicolinate

HRID 244319Notes

Reaction equation

HRID 244319 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][C:16]=1[F:24].[F-].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[C:16]([F:24])[CH:17]=2)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 27786564-Chloro-3-fluorophenylboronic AcidHCID 86668302Methyl 4-amino-6-chloro-5-fluoropicolinate

Product 1

HCID 70498547Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoropicolinateYield 71%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

Methyl 4-amino-6-chloro-5-fluoropicolinate (3.0 g, 14.66 mmol), (4-chloro-3-fluorophenyl)boronic acid (3.07 g, 17.60 mmol), bis(triphenylphosphine)palladium(II) dichloride (1.029 g, 1.466 mmol), and cesium fluoride (4.45 g, 29.3 mmol) were comined in a flask that was sealed and purged with nitrogen. Dioxane (50 ml) and Water (10.00 ml) were added and the reaction mixture was heated at 85° C. for 18 hrs. The reaction mixture was diluted with ethyl acetate and water. The organic phase was washed with saturated sodium chlride, dried over magnesium sulfate, filtered, and concentrated onto silica. The product was purified by flash chromatography (SiO2, 0-40% EtOAc:Hex gradient) to provide the title compound (3.11 g, 10.41 mmol, 71.0% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) d 3.85 (s, 3H), 6.72 (s, 2H), 7.49 (d, J=6.3 Hz, 1H), 7.68-7.80 (m, 2H), 7.84 (dd, J=10.8, 1.3 Hz, 1H); 19F NMR (376 MHz, DMSO-d6) d −144.47, −116.07; ESIMS m/z 299 ([M+H]+).

Workup

  1. customthat was sealed
  2. custompurged with nitrogen
  3. additionDioxane (50 ml) and Water (10.00 ml) were added
  4. additionThe reaction mixture was diluted with ethyl acetate and water
  5. washThe organic phase was washed with saturated sodium chlride
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated onto silica
  9. customThe product was purified by flash chromatography (SiO2, 0-40% EtOAc:Hex gradient)

Sources & evidence

ORD record
ord-27a9f8f056f84a8891d81a0b5c45f50b
Source dataset
uspto-grants-2014_02
Patent number
US08658568B2

Reaction notes

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