Sodium Carbonate → HCID 66993644, compound

HRID 1392652Notes

Reaction equation

HRID 1392652 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[C:5]1[C:10](Cl)=[CH:9][C:8]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:7][C:6]=1[CH3:22])[CH3:2].[CH3:24]B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O.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>[CH2:1]([O:3][C:4](=[O:23])[C:5]1[C:10]([CH3:24])=[CH:9][C:8]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:7][C:6]=1[CH3:22])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 139377Methylboronic AcidHCID 59678345Ethyl 4-chloro-6-(2,6-diethylphenyl)-2-methylnicotinate

Product 1

HCID 66993644HCID 66993644, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-6-(2,6-diethyl-phenyl)-2-methyl-nicotinic acid ethyl ester (0.49 g, 1.5 mmol), methylboronic acid (1.8 g, 29 mmol), and tetrakis(triphenylphosphine)palladium (0.086 g, 0.074 mmol) in toluene (30 mL) is stirred for 10 minutes under N2 atmosphere. A solution of sodium carbonate (6.3 g, 59 mmol) in water (20 mL) is added and the mixture is heated at 100° C. for 48 hours. After cooling to room temperature, the reaction mixture is diluted with water (20 mL) and extracted with EtOAc. The combined extracts are washed with saturated brine, dried (Na2SO4), and concentrated in vacuo. The residue is purified by flash chromatography (elution with hexane/EtOAc 20/1) to give 6-(2,6-diethyl-phenyl)-2,4-dimethyl-nicitinic acid ethyl ester as a colorless oil: 1H NMR (CDCl3) 7.27 (dd, 1H), 7.12 (d, 2H), 6.96 (s, 1H), 4.47 (q, 2H), 2.60 (s, 3H), 2.38 (s, 3H), 2.36-2.28 (m, 4H), 1.45 (t, 3H), 1.05 (t, 6H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with EtOAc
  3. washThe combined extracts are washed with saturated brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by flash chromatography (elution with hexane/EtOAc 20/1)
  7. customto give 6-(2,6-diethyl-phenyl)-2,4-dimethyl-nicitinic acid ethyl ester as a colorless oil

Sources & evidence

ORD record
ord-7763d7a63016446182885579c87f557f
Source dataset
uspto-grants-2008_03
Patent number
US07342115B2

Reaction notes

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