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

HRID 490205Notes

Reaction equation

HRID 490205 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
23 °C

Procedure

A solution of (S)-(+)-2-methylpiperazine (0.50 g, 0.005 mol, CAS 74879-18-8, Aldrich 39,717-2, 99%) and 2-bromopyridine (5 mL, 0.05 mol) was heated to 120° C. for 14 hours. The reaction mixture was cooled to 23° C. and partitioned between ethyl acetate and water. The layers were separated, and the water layer extracted twice more with ethyl acetate. The aqueous phase was adjusted 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 sodium sulfate, filtered, and 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=12, 10 Hz, 1H), 2.67 (m, 3H), 2.92 (m, 1H), 4.07 (m, 2H), 6.58 (dd, J=8, 6 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. custompartitioned between ethyl acetate and water
  2. customThe layers were separated
  3. extractionthe water layer extracted twice more with ethyl acetate
  4. additionSodium chloride was added
  5. extractionthe saturated aqueous solution was extracted with ethyl acetate (2×) and dichloromethane (2×)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-19fe925dda2d4963b9a59290af3b45fe
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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