Water → HCID 66732259, compound

HRID 1963141Notes

Reaction equation

HRID 1963141 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]([F:24])([F:23])[C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].O>CO.C(Cl)Cl.Cl[Pd]Cl>[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[C:18]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 38477682-Bromo-isonicotinic acid methyl ester

Product 1

HCID 66732259HCID 66732259, compoundYield 73.5%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
100 °C

Procedure

Methyl 2-bromoisonicotinate (2.71 g, 12.57 mmol), 3-(trifluoromethyl)phenylboronic acid (3.58 g, 18.85 mmol), potassium carbonate (2.61 g, 18.85 mmol) and PdCl2 (dppf) (0.162 g, 0.25 mmol) were mixed in methanol (30 mL) in two 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. DCM and water were added and the phases 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 added onto an SCX-2 cation exchange column. The column was washed with DCM, MeOH and then eluted with NH3/MeOH (1 CV each). The NH3/MeOH layer was evaporated yielding methyl 2-(3-(trifluoromethyl)phenyl)isonicotinate (2.6 g, 73%). MS m/z 282 (M+H)+

Workup

  1. customThe vials were capped
  2. customthe phases separated
  3. extractionThe water phase (pH 9) was extracted with DCM
  4. washthe combined organic phase washed with brine
  5. customevaporated
  6. customto yield a brown solid
  7. additionadded onto an SCX-2 cation exchange column
  8. washThe column was washed with DCM, MeOH
  9. washeluted with NH3/MeOH (1 CV each)
  10. customThe NH3/MeOH layer was evaporated

Sources & evidence

ORD record
ord-58fd81e4532d4773bf9ea200037134b0
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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