Potassium Carbonate → Methyl 6-(2-cyanophenyl)nicotinate

HRID 602112Notes

Reaction equation

HRID 602112 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O)#[N:13].C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1)#[N:13]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 27346102-Cyanophenylboronic acid

Product 1

HCID 67267132Methyl 6-(2-cyanophenyl)nicotinateYield 14%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Methyl 6-chloronicotinate (1.00 g, 5.83 mmol) and (2-cyanophenyl)boronic acid (856 mg, 5.83 mmol) were added to 1,4-dioxane (50 mL). To this was added 14.6 mL of a 2 M solution of aqueous potassium carbonate and tetrakis(triphenylphosphine)palladium(0) (337 mg, 0.291 mmol). The above reagents were heated at reflux for 5 hours. The reaction was cooled to room temperature and partitioned between ethyl acetate (50 mL) and water (20 mL), the phases were separated and the organic layer was dried over anhydrous MgSO4, filtered and evaporated to a gum. The solid was purified using chromatography on silica eluting with a mixture of heptane: ethyl acetate 80:20, 70:30, 30:70. The product fractions were combined and evaporated to give methyl 6-(2-cyanophenyl)nicotinate as a white solid (195 mg). LCMS (ES+) 239 (M+1), 1.37 minutes; 1H NMR (400 MHz CDCl3) ppm 4.00 (s, 3H) 7.58 (t, J=7.4 Hz, 1H) 7.74 (d, J=6.2 Hz, 1H) 7.85 (d, J=7.8 Hz, 1H) 7.90 (m, 2H) 8.45 (dd, J=5.8, 2.4 Hz, 1H) 9.37 (d, J=2.0, Hz, 1H).

Workup

  1. temperatureThe above reagents were heated
  2. temperatureat reflux for 5 hours
  3. custompartitioned between ethyl acetate (50 mL) and water (20 mL)
  4. customthe phases were separated
  5. dry with materialthe organic layer was dried over anhydrous MgSO4
  6. filtrationfiltered
  7. customevaporated to a gum
  8. customThe solid was purified
  9. additionwith a mixture of heptane: ethyl acetate 80:20, 70:30, 30:70
  10. customevaporated

Sources & evidence

ORD record
ord-a4477fa09d2e444ebb2994fc22e63b04
Source dataset
uspto-grants-2011_03
Patent number
US07902373B2

Reaction notes

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