2-Bromopyridine → HCID 68872849, compound
Reaction equation
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.[Br:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1>>[BrH:8].[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]1Participants
Conditions
- Temperature
- 23 °C
Procedure
A solution of (R)-(−)-2-methylpiperazine (0.50 g, 0.005 mol, CAS 75336-86-6, Aldrich 39,716-4, 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 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 1N Hydrochloric acid solution were added to the water/ethyl acetate mixture with vigorous mixing until all of the product was transferred to the aqueous phase. The layers were separated, and the combined aqueous phases concentrated under reduced pressure, and azeotroped with toluene/methanol (5×) to afford 1.29 g (>99% yield) of 3-(R)-methyl-1-pyridin-2-yl-piperazine hydrobromide. 1H NMR (300 MHz, DMSO-d6) δ 1.27 (d, J=6.6 Hz, 3H), 2.90 (dd, J=10.5, 14.1 Hz, 1H), 3.10 (m, 2H), 3.40 (m, 2H), 4.32 (m, 2H), 6.77 (dd, J=4.8, 6.9 Hz, 1H), 6.98 (d, J=8.1 Hz, 1H), 7.64 (m, 1H), 8.15 (m, 1H), 8.63 (br s, 1H), 8.92 (br s, 1H); MS (ESI) m/e 178 (M+H)+.
Workup
- custompartitioned between a large volume of ethyl acetate and water
- customThe layers were separated
- additionadditional water was added to the ethyl acetate solution
- additionDrops of 1N Hydrochloric acid solution were added to the water/ethyl acetate mixture
- additionwith vigorous mixing until all of the product
- customThe layers were separated
- concentrationthe combined aqueous phases concentrated under reduced pressure
- customazeotroped with toluene/methanol (5×)
Sources & evidence
- ORD record
- ord-f7125861cde944b6b367f7b9fa9c12c9
- Source dataset
- uspto-grants-2009_05
- Patent number
- US07528134B2
Reaction notes
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