Hydrochloric Acid → 6-(3-Ethoxyphenyl)nicotinic acid

HRID 388382Notes

Reaction equation

HRID 388382 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.[CH2:11]([O:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1)[CH3:12].C(=O)([O-])[O-].[Na+].[Na+].Cl>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.C(OCC)(=O)C>[CH2:11]([O:13][C:14]1[CH:19]=[C:18]([C:2]2[N:7]=[CH:6][C:5]([C:8]([OH:10])=[O:9])=[CH:4][CH:3]=2)[CH:17]=[CH:16][CH:15]=1)[CH3:12]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 2389326-Bromonicotinic acidHCID 27739203-Ethoxybenzeneboronic acid

Product 1

HCID 532232596-(3-Ethoxyphenyl)nicotinic acidYield 24.1%

Reagents, catalysts & solvents 4

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 6-bromo-3-pyridinecarboxylic acid (Sigma-Aldrich; 100 mg, 0.495 mmol) in 1,2-dimethoxyethane (9 ml) was added [3-(ethyloxy)phenyl]boronic acid (Sigma-Aldrich; 247 mg, 1.485 mmol), sodium carbonate (315 mg, 2.97 mmol) pre-dissolved in water (1 ml) and bis(triphenylphosphine)palladium(II)chloride (52.1 mg, 0.074 mmol). The mixture was heated at 140° C. for 30 mins in a microwave reactor (high absorbance). Ethyl acetate and water were added followed by aqueous HCl (5M). The aqueous layer was extracted with more ethyl acetate. The organic layers were evaporated to dryness and purified using a 5 g SAX column which was pre conditioned with MeOH. The column was washed with MeOH (2 column volumes) and then eluted with 0.5M NH3/MeOH. The eluant was evaporated to dryness under reduced pressure to give a yellow solid. Purification by MDAP gave the title compound as a white solid (29 mg);

Workup

  1. extractionThe aqueous layer was extracted with more ethyl acetate
  2. customThe organic layers were evaporated to dryness
  3. custompurified
  4. washThe column was washed with MeOH (2 column volumes)
  5. washeluted with 0.5M NH3/MeOH
  6. customThe eluant was evaporated to dryness under reduced pressure
  7. customto give a yellow solid
  8. customPurification by MDAP

Sources & evidence

ORD record
ord-0fa15fd94730425abcd669c6040a1d54
Source dataset
uspto-grants-2013_02
Patent number
US08377941B2

Reaction notes

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