Methanol → (2,6-Difluoro-phenyl)-[4-(6-methyl-5-nitro-pyridin-2-yl)-piperazin-1-yl]-methanone

HRID 1993650Notes

Reaction equation

HRID 1993650 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]([N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)=[O:10].CO.C(N(CC)CC)C.Cl[C:27]1[N:32]=[C:31]([CH3:33])[C:30]([N+:34]([O-:36])=[O:35])=[CH:29][CH:28]=1>O>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]([N:11]1[CH2:12][CH2:13][N:14]([C:27]2[CH:28]=[CH:29][C:30]([N+:34]([O-:36])=[O:35])=[C:31]([CH3:33])[N:32]=2)[CH2:15][CH2:16]1)=[O:10]

Participants

6

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 2531236-Chloro-2-methyl-3-nitropyridineHCID 183627501-(2,6-Difluorobenzoyl)piperazine

Product 1

HCID 68537965(2,6-Difluoro-phenyl)-[4-(6-methyl-5-nitro-pyridin-2-yl)-piperazin-1-yl]-methanoneYield 101.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Charge (2,6-difluoro-phenyl)-piperazin-1-yl-methanone (1.07 equiv, 1.55 moles, 350.00 g), methanol (37.06 moles, 1.50 L, 1.19 kg), triethylamine (1.79 moles, 250.00 mL, 181.50 g), 6-chloro-2-methyl-3-nitro-pyridine (1.00 equiv, 1.45 moles, 250.00 g) to a 5 L flask with over head stirrer. Stir the reaction mixture at room temperature for 0.5 hours. Slowly heat to 60° C., and continue to stir at 60° C. overnight. Add water (750 mL) drop wise while maintaining the temperature at 60° C. Allow mixture to cool to room temperature. Filter and wash cake with 2:1 methanol/water 150 mL, then twice with MTBE. Dry under reduced pressure at 45° C. to obtain (2,6-difluoro-phenyl)-[4-(6-methyl-5-nitro-pyridin-2-yl)-piperazin-1-yl]-methanone as a yellow solid (535 g).

Workup

  1. temperatureSlowly heat to 60° C.
  2. stirringto stir at 60° C. overnight
  3. temperatureto cool to room temperature
  4. filtrationFilter
  5. washwash cake with 2:1 methanol/water 150 mL
  6. customDry under reduced pressure at 45° C.

Sources & evidence

ORD record
ord-056920826bfd4501988fac6cb0ca97fb
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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