Water → 5-Cyclopropyl-6-(1,1,1-trifluoropropan-2-yloxy)picolinic acid

HRID 624863

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([C:15]([OH:17])=[O:16])=[N:6][C:7]=1[O:8][CH:9]([CH3:14])[C:10]([F:13])([F:12])[F:11].[CH:18]1([B-](F)(F)F)[CH2:20][CH2:19]1.[K+].C(=O)([O-])[O-].[Cs+].[Cs+].O>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(PC12CC3CC(CC(C3)C1)C2)CCC>[CH:18]1([C:2]2[CH:3]=[CH:4][C:5]([C:15]([OH:17])=[O:16])=[N:6][C:7]=2[O:8][CH:9]([CH3:14])[C:10]([F:13])([F:12])[F:11])[CH2:20][CH2:19]1

Participants

Conditions

Temperature: 120 °C

Procedure

5-Bromo-6-(1,1,1-trifluoropropan-2-yloxy)picolinic acid (2 g, 6.37 mmol), potassium cyclopropyltrifluoroborate (952 mg, 6.43 mmol), cesium carbonate (6.22 g, 19.1 mmol) and palladium(II)acetate (28.6 mg, 127 μmol) were suspended in toluene (55 mL) and water (6.11 mL) under an argon atmosphere. Butyl-1-adamantylphosphin (68.5 mg, 191 μmol) was added, the reaction mixture was heated to 120° C. for 1 d, poured onto ice-water/1N HCl (150 mL) and extracted with EtOAc (2×300 mL). The combined organic layers were washed with ice-water/brine (150 mL), dried over Na2SO4 and concentrated in vacuo to give the title compound (1.38 g, 79%) as a yellow solid. MS (EI): m/e=276.2 [M+H]+.

Workup

additionpoured onto ice-water/1N HCl (150 mL)
extractionextracted with EtOAc (2×300 mL)
washThe combined organic layers were washed with ice-water/brine (150 mL)
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-f8f51eff5cd34051872e2767fc006127
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09303012B2

Linked notes

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