Potassium Carbonate → Methyl 2-(4-chlorophenyl)nicotinate

HRID 1058318Notes

Reaction equation

HRID 1058318 reaction equation
Br[C:2]1[N:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Cl:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[N:11]=[CH:10][CH:9]=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 12349191Methyl 2-bromopyridine-3-carboxylate

Product 1

HCID 15318002Methyl 2-(4-chlorophenyl)nicotinateYield 93.5%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a solution of methyl 2-bromonicotinate (5.6 g, 25.9 mmol) in toluene (140 mL) was added 4-chlorophenylboronic acid (6.1 g, 38.9 mmol), potassium carbonate (5.4 g, 39 mmol), and tetrakis(triphenylphosphine) palladium (1.53 g. 1.3 mmol). The mixture was heated to reflux for 3.5 hours, evaporated in vacuo and then purified on a silica gel column using a 1:4 mixture of ethyl acetate:hexane as mobile phase. Pure fractions were combined and the solvent was removed in vacuo to yield methyl 2-(4-chlorophenyl)nicotinate (6.0 g, HPLC RT=3.04 min, method A; LC-MS m/z=248).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 3.5 hours
  3. customevaporated in vacuo
  4. custompurified on a silica gel column
  5. additiona 1:4 mixture of ethyl acetate
  6. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-19fd726250af49daa1609b2c45afad92
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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