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

HRID 2110119Notes

Reaction equation

HRID 2110119 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) δ 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-dea9cef584184f60852c15b087b53272
Source dataset
uspto-grants-2009_04
Patent number
US07517884B2

Reaction notes

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