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

HRID 632452

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+].Cl>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(PC12CC3CC(CC(C3)C1)C2)CCC.O>[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 icewater/1N HCl (150 mL) and extracted with EtOAc (2×300 mL). The combined organic layers were washed with icewater/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

extractionextracted with EtOAc (2×300 mL)
washThe combined organic layers were washed with icewater/brine (150 mL)
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-ae0dddf6dcb44928a58fb06af65a7bda
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321727B2

Linked notes

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