Acrylic Acid → (2E)-3-(6-aminopyridin-3-yl)prop-2-enoic acid

HRID 1361929Notes

Reaction equation

HRID 1361929 reaction equation
[C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3].[NH2:6][C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][N:8]=1.C([O-])([O-])=O.[Na+].[Na+]>O.Cl[Pd]Cl>[NH2:6][C:7]1[N:8]=[CH:9][C:10](/[CH:3]=[CH:2]/[C:1]([OH:5])=[O:4])=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 6581Acrylic AcidHCID 10340Sodium CarbonateHCID 706222-Amino-5-bromopyridine

Product 1

HCID 10487224(2E)-3-(6-aminopyridin-3-yl)prop-2-enoic acidYield 62.5%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolvent

Procedure

Acrylic acid (23 mL, 0.33 mole) was added carefully to a solution of 2-amino-5-bromopyridine (25.92 g, 0.15 mole) and Na2CO3 (55.64 g, 0.53 mole) in H2O (600 mL). PdCl2 (0.53 g, 0.003 mole) was then added, and the mixture was heated at reflux. After 24 hr, the reaction was cooled to RT and filtered, and the filtrate was adjusted to pH 6 with aqueous HCl. Additional H2O (0.5 L) was added to improve mixing, and the mixture was stirred for 1 hr. The pH was readjusted to 6, then the solid was collected by suction filtration. The filter pad was washed sequentially with H2O (2×0.5 L), cold absolute EtOH (100 mL), and Et2O (2×250 mL). Drying in high vacuum at elevated temperature gave the title compound (15.38 g, 62%) as a tan solid: 1H NMR (300 MHz, DMSO-d6) δ 8.11 (d, J=2.0 Hz, 1H), 7.75 (dd, J=8.7, 2.0 Hz, 1H), 7.43 (d, J=15.8 Hz, 1H), 6.53 (s, 2H), 6.45 (d, J=8.7 Hz, 1H), 6.22 (d, J=15.8 Hz, 1H); MS (ES) m/e 165 (M+H)+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux
  3. filtrationfiltered
  4. additionAdditional H2O (0.5 L) was added
  5. additionto improve mixing
  6. filtrationthe solid was collected by suction filtration
  7. washThe filter pad was washed sequentially with H2O (2×0.5 L), cold absolute EtOH (100 mL), and Et2O (2×250 mL)
  8. customDrying in high vacuum at elevated temperature

Sources & evidence

ORD record
ord-8558d6f0d3dd4b03b286e80ab5aed2a1
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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