Methane → 5-Bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)pyridine

HRID 1071182Notes

Reaction equation

HRID 1071182 reaction equation
[CH3:1][C:2](=O)[CH2:3][CH2:4][C:5](=O)[CH3:6].[NH2:9][C:10]1[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][N:11]=1.C>C1CCCCC1.C(O)(=O)C>[Br:16][C:13]1[CH:14]=[CH:15][C:10]([N:9]2[C:2]([CH3:1])=[CH:3][CH:4]=[C:5]2[CH3:6])=[N:11][CH:12]=1

Participants

6

Reactant 3

HCID 297MethaneHCID 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 2

HCID 176Acetic AcidSolventHCID 8078CyclohexaneSolvent

Procedure

Hexane-2,5-dione (97 mL, 831 mmol) was added to a solution of 2-amino-5-bromo-pyridine (125 g, 722 mmol) in cyclohexane (625 mL) and acetic acid (20 mL). The solution was heated to reflux under argon atmosphere with a Dean-Stark trap. A total of 30 mL of water was collected from the Dean-Stark trap. The mixture was allowed to cool to room temperature, diluted with water, and extracted with diethyl ether. The organic phase was washed with 1 N hydrochloric acid (4×), saturated aqueous sodium bicarbonate solution (2×) and saturated aqueous sodium chloride solution (2×). The organic phase was dried (MgSO4) and concentrated in vacuo to yield a yellow solid. The product was dissolved in hot hexanes (200 mL). Charcoal was added and the mixture filtered. Crystallization proceeded over three hours at 0° C. The solid was collected by filtration to yield yellow crystals (145 g, 80%). Mp=69° C.; 1H NMR (CDCl3, 300 MHz) δ 8.66 (d, 9 Hz, 1H), 7.96 (dd, 9 Hz, 8 Hz, 1H), 7.15 (d, 8 Hz, 1H), 5.91 (s, 2H), 2.14 (s, 6H); MS (CI) m/z 251 (MH+); Anal. Calcd. for C11H11BrN2: C, 52.61; H, 4.42; N, 11.16; Br, 31.82. Found: C, 52.62; H, 4.56; N, 11.18; Rf=0.4 (60:40 dichloromethane/hexanes).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux under argon atmosphere with a Dean-Stark trap
  3. customA total of 30 mL of water was collected from the Dean-Stark trap
  4. additiondiluted with water
  5. extractionextracted with diethyl ether
  6. washThe organic phase was washed with 1 N hydrochloric acid (4×), saturated aqueous sodium bicarbonate solution (2×) and saturated aqueous sodium chloride solution (2×)
  7. dry with materialThe organic phase was dried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto yield a yellow solid
  10. filtrationthe mixture filtered
  11. customCrystallization
  12. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-a2cde2511eb04efc9e61607d025ecd56
Source dataset
uspto-grants-2005_06
Patent number
US06903218B2

Reaction notes

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