2-Bromopyridine → (3R)-3-methyl-1-pyridin-2-ylpiperazine

HRID 898719Notes

Reaction equation

HRID 898719 reaction equation
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.Br[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1>>[CH3:1][C@H:2]1[NH:3][CH2:4][CH2:5][N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH2:7]1

Participants

3

Reactant 2

HCID 79732-BromopyridineHCID 73304342-Methylpiperazine, (R)-

Product 1

HCID 1519493(3R)-3-methyl-1-pyridin-2-ylpiperazineYield 89.1%

Conditions

Temperature
120 °C

Procedure

(R)-(−)-2-Methylpiperazine (0.50 g, 0.005 mol, Aldrich) and 2-bromopyridine (5 mL, 0.05 mol) were combined and heated at 120° C. for 14 hours. The reaction mixture was allowed to cool to 23° C. and partitioned between a large volume of ethyl acetate and water. The layers were separated, and then additional water was added to the ethyl acetate solution. Drops of 1 N HCl solution were added to the water/ethyl acetate mixture with vigorous mixing. The layers were separated, and the combined aqueous phases were basified to pH ˜11 with a solution of saturated sodium bicarbonate and solid sodium carbonate. Sodium chloride was added, and the saturated aqueous solution was extracted with chloroform containing a few drops of isopropyl alcohol (5×). The combined organic extracts were dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure to afford 0.79 g (89% yield) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 1.02 (d, J=6.0 Hz, 3H), 2.27 (dd, J=10, 12 Hz, 1), 2.67 (m, 3H), 2.92 (m, 1H), 4.07 (m, 2H), 6.58 (dd, J=6, 8 Hz, 1H), 6.77 (d, J=8 Hz, 1H), 7.49 (m, 1H), 8.08 (m, 1H); MS (ESI) m/e 178 (M+H)+.

Workup

  1. temperatureto cool to 23° C.
  2. custompartitioned between a large volume of ethyl acetate and water
  3. customThe layers were separated
  4. additionadditional water was added to the ethyl acetate solution
  5. additionDrops of 1 N HCl solution were added to the water/ethyl acetate mixture with vigorous mixing
  6. customThe layers were separated
  7. additionSodium chloride was added
  8. extractionthe saturated aqueous solution was extracted with chloroform containing a few drops of isopropyl alcohol (5×)
  9. dry with materialThe combined organic extracts were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationthe filtrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-f3f3fcaa6e104ee3bae73689fea48532
Source dataset
uspto-grants-2008_04
Patent number
US07351828B2

Reaction notes

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