Sodium Carbonate → Methyl 2-(4-fluorophenyl)nicotinate

HRID 2360723Notes

Reaction equation

HRID 2360723 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[CH3:7][O:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[N:12][C:11]=1Cl.[F:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1>CCO>[CH3:7][O:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[N:12][C:11]=1[C:22]1[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 819931Methyl 2-chloronicotinate

Product 1

HCID 15318001Methyl 2-(4-fluorophenyl)nicotinate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
78 °C

Procedure

To a nitrogen purged flask was charged Pd(Ph3)4 (1.84 g, 1.6 mmoles, 0.005 eq), sodium carbonate (42.8 g, 404 mmoles, 1.3 eq), 52 (55.5 g, 320.6 mmoles, 1.0 eq), p-fluorophenylboronic acid (53.8 g, 384.7 mmoles, 1.2 eq), followed by 1.3 L denatured EtOH. The reaction was heated to 78° C. with vigorous stirring under N2 overnight. HPLC analysis [Tret 52=10 min, Tret 54=12 min] of the reaction mixture showed that the starting material was completely consumed and a later-eluting peak produced. The reaction was cooled to room temperature and the solvents removed under vacuum. The residue was dissolved in EtOAc, washed, dried (MgSO4), filtered through celite, and concentrated to afford a pale yellow solid 54.

Workup

  1. customHPLC analysis [Tret 52=10 min, Tret 54=12 min] of the reaction mixture
  2. customwas completely consumed
  3. customa later-eluting peak produced
  4. temperatureThe reaction was cooled to room temperature
  5. customthe solvents removed under vacuum
  6. dissolutionThe residue was dissolved in EtOAc
  7. washwashed
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered through celite
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-85da213c95db4ef18d60c8dda19038e7
Source dataset
uspto-grants-2014_04
Patent number
US08686157B2

Reaction notes

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