Potassium Phosphate, Tribasic → Methyl 2-chloro-5-methylnicotinate

HRID 2362831Notes

Reaction equation

HRID 2362831 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([Cl:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:21]B(O)O.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:12][C:5]1[N:4]=[CH:3][C:2]([CH3:21])=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 139377Methylboronic AcidHCID 2763343Methyl 5-bromo-2-chloronicotinate

Product 1

HCID 11636946Methyl 2-chloro-5-methylnicotinateYield 87%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22272177Toluene waterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 5-bromo-2-chloronicotinate (1.05 g, 4.19 mmol), K3PO4 (2.95 g, 13.90 mmol), methylboronic acid (0.32 g, 5.26 mmol) and tricyclohexylphosphine (0.11 g, 0.39 mmol) in toluene/water (16 ml/0.8 ml) under nitrogen atmosphere was added Pd(OAc)2 (0.04 g, 0.18 mmol). The mixture was heated at 100° C. overnight under nitrogen atmosphere. The reaction mixture was then cooled to room temperature and concentrated in vacuum. Ethyl acetate was added to the residue and this organic layer was washed with water, brine, dried over MgSO4, filtered and the solvent evaporated under vacuum to yield the desired product as a yellow oil. Yield=87%

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. concentrationconcentrated in vacuum
  3. additionEthyl acetate was added to the residue
  4. washthis organic layer was washed with water, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvent evaporated under vacuum

Sources & evidence

ORD record
ord-d61d719392be4cc985e63d5953c671ed
Source dataset
uspto-grants-2014_04
Patent number
US08691852B2

Reaction notes

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