Dichloromethane → Methyl 2-Phenylisonicotinate

HRID 1963227Notes

Reaction equation

HRID 1963227 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:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>CO.O.Cl[Pd]Cl>[C:12]1([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]=[CH:14][CH:13]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 2736842Methyl 2-chloropyridine-4-carboxylate

Product 1

HCID 12183945Methyl 2-PhenylisonicotinateYield 58.9%

Reagents, catalysts & solvents 4

HCID 962WaterCatalystHCID 24290Palladium ChlorideCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (2.5 g, 14.57 mmol), phenylboronic acid (2.66 g, 21.86 mmol), potassium carbonate (3.02 g, 21.86 mmol) and PdCl2 (dppf) (0.316 g, 0.44 mmol) were mixed in methanol (15 mL) in a 20 mL microwave vial. Two drops of water were added and the vial was capped and heated at 100° C. for 10 min in a single node microwave reactor. The solids were removed by filtration and the filtrate partly evaporated to yield a dark red slurry. 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 dark red oil. The compound was purified via Biotage, SNAP 340 g KP-SIL, eluent isocratic heptane/ethyl acetate 9:1 for 2 CV, then linear gradient heptane/ethyl acetate 9:1 to 6:4 over 5 CV to give methyl 2-phenylisonicotinate (1.83 g, 58%) as a colourless oil. 1H NMR (400 MHz, cdcl3) δ 3.98 (s, 3H), 7.39-7.54 (m, 3H), 7.76 (dd, 1H), 8.01-8.09 (m, 2H), 8.29 (s, 1H), 8.82 (d, 1H). MS m/z 214 (M+H)+

Workup

  1. customthe vial was capped
  2. customThe solids were removed by filtration
  3. customthe filtrate partly evaporated
  4. customto yield a dark red slurry
  5. customthe phases separated
  6. extractionThe water phase (pH 9) was extracted with DCM
  7. washthe combined organic phase washed with brine
  8. customevaporated
  9. customto yield a dark red oil
  10. customThe compound was purified via Biotage, SNAP 340 g KP-SIL, eluent isocratic heptane/ethyl acetate 9:1 for 2 CV

Sources & evidence

ORD record
ord-98e5eb00824f4e719b8ba42c2812c9a7
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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