p-Toluenesulfonic acid → 5-Bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)pyridine

HRID 1781982Notes

Reaction equation

HRID 1781982 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH3:9][C:10](=O)[CH2:11][CH2:12][C:13](=O)[CH3:14].C1(C)C=CC(S(O)(=O)=O)=CC=1>CCCCCCC>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([N:1]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]2[CH3:9])=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80352,5-HexanedioneHCID 706222-Amino-5-bromopyridine

Product 1

HCID 120436225-Bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)pyridineYield 80%

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Conditions

Temperature
20 °C

Procedure

2-Amino-5-bromopyridine (6.0 Kg, 34.7 mol), 2,5-hexanedione (4.35 Kg, 38.2 mol) and p-toluenesulfonic acid (12 g) were dissolved in heptane (36 L) and refluxed under Dean Stark conditions overnight. The equipment was set for distillation and heptane (18 L) was removed by distillation. The mixture was cooled to 20° C. for 60 minutes. Seed crystals were added and the mixture granulated at 20° C. for 2 hours and then at 5° C. overnight. The product was collected by filtration, washed with heptane (2×6 L) and dried at 45° C. under vacuum overnight. Yield=80% (7.0 Kg) δH (CDCl3 300 MHz) 2.20 (6H, s), 5.95 (2H, s), 7.15 (1H, d), 7.95 (1H, d), 8.70 (1H, s) ppm. MS m/z 253 (MH+, Br isotope).

Workup

  1. temperaturerefluxed under Dean Stark conditions overnight
  2. distillationThe equipment was set for distillation and heptane (18 L)
  3. customwas removed by distillation
  4. additionSeed crystals were added
  5. customat 5° C.
  6. customovernight
  7. filtrationThe product was collected by filtration
  8. washwashed with heptane (2×6 L)
  9. customdried at 45° C. under vacuum overnight

Sources & evidence

ORD record
ord-1a09d052e34b42498da108bf302c1b78
Source dataset
uspto-grants-2009_03
Patent number
US07498329B2

Reaction notes

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