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

HRID 1794213Notes

Reaction equation

HRID 1794213 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 27342192-Methylpiperazine, (S)-

Product 1

HCID 1519492(3S)-3-methyl-1-pyridin-2-ylpiperazineYield 67.7%

Conditions

Temperature
120 °C

Procedure

(S)-(+)-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 ethyl acetate and water. The layers were separated, and the water layer extracted twice with ethyl acetate. The aqueous phase was brought 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 ethyl acetate (2×) and dichloromethane (2×). The combined organic extracts were dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure to afford 0.6 g (67% 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 ethyl acetate and water
  3. customThe layers were separated
  4. extractionthe water layer extracted twice with ethyl acetate
  5. additionSodium chloride was added
  6. extractionthe saturated aqueous solution was extracted with ethyl acetate (2×) and dichloromethane (2×)
  7. dry with materialThe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-358a7d8be642459f919e23659e5061d6
Source dataset
uspto-grants-2006_04
Patent number
US07022728B2

Reaction notes

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