Potassium Carbonate → Methyl 2-(3,4,5-trifluorophenyl)isonicotinate

HRID 1963196Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[F:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[C:17]([F:20])[C:18]=1[F:19].C(=O)([O-])[O-].[K+].[K+]>CO.C(Cl)Cl.Cl[Pd]Cl>[F:12][C:13]1[CH:14]=[C:15]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH:16]=[C:17]([F:20])[C:18]=1[F:19]

Participants

Conditions

Temperature: 100 °C

Procedure

Methyl 2-bromoisonicotinate (4 g, 18.52 mmol), 3,4,5-trifluorophenylboronic acid (4.89 g, 27.77 mmol), potassium carbonate (3.84 g, 27.77 mmol) and PdCl2 (dppf) (0.402 g, 0.56 mmol) were mixed in methanol (30 mL) in two separate 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. Water and DCM were added and the phases were separated. The water phase (pH 9) was extracted with DCM and the combined organic phase washed with brine, passed through a phase separator and evaporated to yield a brown solid. The residue was dissolved in DCM and purified by SCX-2 cation exchange chromatography. Methyl 2-(3,4,5-trifluorophenyl)isonicotinate (2.62 g, 52%) was isolated as a slightly yellow solid. MS m/z 268 (M+H)+

Workup

customseparate 20 mL microwave vials
customThe vials were capped
additionWater and DCM were added
customthe phases were separated
extractionThe water phase (pH 9) was extracted with DCM
washthe combined organic phase washed with brine
customevaporated
customto yield a brown solid
custompurified by SCX-2 cation exchange chromatography

Sources & evidence

ORD record: ord-5c8f2e49c53b41fd866ec5ae6c644456
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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