Potassium Fluoride → Methyl 4-amino-3-chloro-6-(3-fluoro-4-(trifluoromethyl)phenyl)picolinate

HRID 516550Notes

Reaction equation

HRID 516550 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[Cl:13].[F:14][C:15]1[CH:16]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:18]=[CH:19][C:20]=1[C:21]([F:24])([F:23])[F:22].[F-].[K+]>C(#N)C.O.C(OCC)(=O)C.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[CH:7]=[C:6]([C:17]2[CH:18]=[CH:19][C:20]([C:21]([F:23])([F:24])[F:22])=[C:15]([F:14])[CH:16]=2)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[Cl:13]

Participants

7

Reactant 3

HCID 522689Potassium FluorideHCID 22677331Methyl 4-amino-3,6-dichloropyridine-2-carboxylateHCID 467390543-Fluoro-4-(trifluoromethyl)phenylboronic acid pinacol ester

Product 1

HCID 90409861Methyl 4-amino-3-chloro-6-(3-fluoro-4-(trifluoromethyl)phenyl)picolinateYield 57.4%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

Methyl 4-amino-3,6-dichloropicolinate (630 mg, 2.85 mmol), 2-(3-fluoro-4-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.06 g, 3.65 mmol, 1.3 equiv), bis(triphenylphosphine)palladium(II) chloride (209 mg, 0.30 mmol, 0.1 equiv), and potassium fluoride (510 mg, 8.8 mmol, 3 equiv) in acetonitrile/water (8 mL, 3:1) was capped in a 25-mL vial on a Biotage Initiator™ microwave reactor for 20 min at 115° C., with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude compound was loaded onto a Celite™ cartridge and dried in vacuum oven. Purification by reverse-phase flash chromatography (0-60, 60, 60-100% acetonitrile/water) afforded the title compound as a white solid (0.57 g, 57%).

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customdried in vacuum oven
  7. customPurification by reverse-phase flash chromatography (0-60, 60, 60-100% acetonitrile/water)

Sources & evidence

ORD record
ord-0f849c1f5d18405e85e02b41ae6fcc65
Source dataset
uspto-grants-2015_08
Patent number
US09113629B2

Reaction notes

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