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

HRID 1963192Notes

Reaction equation

HRID 1963192 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].[F:12][C:13]1[CH:18]=[C:17]([O:19][C:20]([F:23])([F:22])[F:21])[CH:16]=[CH:15][C:14]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+]>CO.Cl[Pd]Cl>[F:12][C:13]1[CH:18]=[C:17]([O:19][C:20]([F:21])([F:22])[F:23])[CH:16]=[CH:15][C:14]=1[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 594152212-[2-Fluoro-4-(trifluoromethoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 66731729Methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)isonicotinateYield 81.3%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (3 g, 17.48 mmol), 2-(2-fluoro-4-(trifluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.37 g, 17.55 mmol), potassium carbonate (1.812 g, 13.11 mmol) and PdCl2 (dppf) (0.380 g, 0.52 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 aqueous phase was extracted with DCM and the combined organic layers were filtered through a phase separator and evaporated to yield a dark-brown solid. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column. A gradient from 8:1 to 3:1 of EtOAc in heptane over 10 CV was used as mobile phase. Methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)isonicotinate (4.48 g, 81%) was yielded as a colorless solid. 1H NMR (600 MHz, cdcl3) δ 3.96 (s, 3H), 7.07 (d, 1H), 7.14 (d, 1H), 7.79-7.84 (m, 1H), 8.03-8.09 (m, 1H), 8.31 (s, 1H), 8.82-8.88 (m, 1H). MS m/z 316 (M+H)+

Workup

  1. customseparate 20 mL microwave vials
  2. customThe vials were capped
  3. additionWater and DCM were added
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted with DCM
  6. filtrationthe combined organic layers were filtered through a phase separator
  7. customevaporated
  8. customto yield a dark-brown solid
  9. customThe residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column

Sources & evidence

ORD record
ord-6ff1f1f6cf334560811b55c42bf2b799
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…