Toluene → Ethyl 2-(2,4-difluorophenyl)pyridine-3-carboxylate

HRID 2390945Notes

Reaction equation

HRID 2390945 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Cl[C:8]1[N:18]=[CH:17][CH:16]=[CH:15][C:9]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11].[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1B(O)O.C1(C)C=CC=CC=1>CCO>[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[C:8]1[N:18]=[CH:17][CH:16]=[CH:15][C:9]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

6

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 2796614Ethyl chloronicotinate

Product 1

HCID 21062877Ethyl 2-(2,4-difluorophenyl)pyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
82 °C

Procedure

To a nitrogen purged 3.0 L, 4-necked flask, fitted with an overhead stirrer, thermocouple, heating mantle, nitrogen outlet and reflux condenser, was charged Pd(Ph3)4 (5.0 g, 4.33 mmoles, 0.005 eq), sodium carbonate (92.6 g, 874 mmoles, 1.3 eq), ethyl 2-chloronicotinate, 1 (126.0 g, 678 moles, 1.0 eq), 2,4-difluorophenylboronic acid, 2 (125 g, 791 mmoles, 1.2 eq), followed by 0.5 L of toluene and 125 mL denatured EtOH. The reaction was heated to 82° C. with vigorous stirring under N2 overnight (completeness of reaction determined by HPLC and TLC). The reaction was cooled to room temperature, the mixture filtered through a small pad of Celite® and the solvents removed under vacuum at 55° C. The residue was dissolved in EtOAc, washed, dried (MgSO4), filtered through Celite® again, and concentrated. The product was obtained as a yellow solid.

Workup

  1. customTo a nitrogen purged 3.0 L, 4-necked flask
  2. customfitted with an overhead stirrer
  3. temperaturethermocouple, heating mantle, nitrogen outlet
  4. temperaturereflux condenser
  5. custom(completeness of reaction determined by HPLC and TLC)
  6. temperatureThe reaction was cooled to room temperature
  7. filtrationthe mixture filtered through a small pad of Celite®
  8. customthe solvents removed under vacuum at 55° C
  9. dissolutionThe residue was dissolved in EtOAc
  10. washwashed
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered through Celite® again
  13. concentrationconcentrated
  14. customThe product was obtained as a yellow solid

Sources & evidence

ORD record
ord-f5a5a3710a7346e8ae5b33df19e1afda
Source dataset
uspto-grants-2012_09
Patent number
US08273896B2

Reaction notes

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