Triethylamine → (S)-3-methyl-1-(5-(trifluoromethyl)pyridin-2-yl)piperazine

HRID 605523Notes

Reaction equation

HRID 605523 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=1.[CH3:12][C@H:13]1[CH2:18][NH:17][CH2:16][CH2:15][NH:14]1.C(N(CC)CC)C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:12][C@@H:13]1[NH:14][CH2:15][CH2:16][N:17]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=2)[CH2:18]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27342192-Methylpiperazine, (S)-HCID 27364342-Bromo-5-(trifluoromethyl)pyridine

Product 1

HCID 26597362(S)-3-methyl-1-(5-(trifluoromethyl)pyridin-2-yl)piperazineYield 81%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Bromo-5-trifluoromethyl-pyridine (1.06 g, 4.69 mmol), (S)-2-methylpiperazine (1.03 g, 10.28 mmol) and triethylamine (1.5 mL, 10.76 mmol) were stirred in toluene (10 mL) at 110° C. for 26 h. The reaction was cooled to room temperature, diluted with ethyl acetate (150 mL) and washed with water and brine. The organic layer was dried (MgSO4), filtered and concentrated. The crude mixture was purified by automated silica gel flash column chromatography (gradient eluent 0-20% MeOH/dichloromethane) to afford 3-(S)-methyl-1-(5-trifluoromethyl-pyridin-2-yl)-piperazine (926 mg, 81%) as a yellow solid. 1H NMR (400 MHz, CDCl3) 8.38 (s, 1H), 7.62 (dd, 1H), 7.63 (d, 1H), 4.29-4.20 (m, 2H), 3.16-3.12 (m, 1H), 3.02-2.85 (m, 3H), 2.64-2.52 (m, 2H), 1.18 (d, 3H).

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude mixture was purified by automated silica gel flash column chromatography (gradient eluent 0-20% MeOH/dichloromethane)

Sources & evidence

ORD record
ord-917cb9a905f24ca0aa03ed6c5329ffaf
Source dataset
uspto-grants-2011_03
Patent number
US07915253B2

Reaction notes

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