Potassium Carbonate → Methyl 2-(3-fluoro-4-(trifluoromethyl)phenyl)isonicotinate

HRID 1963223Notes

Reaction equation

HRID 1963223 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[K+].[K+].[F:18][C:19]1[CH:20]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:22]=[CH:23][C:24]=1[C:25]([F:28])([F:27])[F:26]>CO.Cl[Pd]Cl>[F:18][C:19]1[CH:20]=[C:21]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH:22]=[CH:23][C:24]=1[C:25]([F:26])([F:27])[F:28]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 467390543-Fluoro-4-(trifluoromethyl)phenylboronic acid pinacol ester

Product 1

HCID 66732503Methyl 2-(3-fluoro-4-(trifluoromethyl)phenyl)isonicotinateYield 76.1%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (2.86 g, 16.67 mmol), PdCl2 (dppf) (0.278 g, 0.38 mmol) and potassium carbonate (1.161 mL, 19.24 mmol) were distributed equally over 3 microwave reaction vials. 2-(3-Fluoro-4-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-borolane (3.72 g, 12.82 mmol) dissolved in methanol (45 mL) was split into 3 equal portions and added to the vials. The vials were capped and heated in a single node microwave reactor at 100° C. for 10 min each. The contents of the vials was combined and the solvent evaporated. The residue was dissolved in DCM and washed with water. The organic phase was filtered through a phase separator and evaporated. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column. 7:1 of heptane:EtOAc over 10 CV was used as mobile phase. Crude methyl 2-(3-fluoro-4-(trifluoromethyl)phenyl)isonicotinate (2.92 g, 76%) was isolated. MS m/z 300 (M+H)+

Workup

  1. customwas split into 3 equal portions
  2. additionadded to the vials
  3. customThe vials were capped
  4. customthe solvent evaporated
  5. dissolutionThe residue was dissolved in DCM
  6. washwashed with water
  7. filtrationThe organic phase was filtered through a phase separator
  8. customevaporated
  9. customThe residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column

Sources & evidence

ORD record
ord-284d82b5404541aa96bfc01eee69f6a0
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…