Potassium Carbonate → 2-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-nitrotoluene

HRID 1027976Notes

Reaction equation

HRID 1027976 reaction equation
[CH3:1][N:2]1[CH:6]2[CH2:7][NH:8][CH:4]([CH2:5]2)[CH2:3]1.Cl.Cl.F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[CH3:21].C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[CH3:1][N:2]1[CH2:3][C@@H:4]2[CH2:5][C@H:6]1[CH2:7][N:8]2[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[CH3:21]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 68001Benzene, 1-fluoro-2-methyl-4-nitro-HCID 229244032-Methyl-2,5-diaza-bicyclo[2.2.1]heptane dihydrochloride

Product 1

HCID 686324012-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-nitrotolueneYield 74.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Alternatively, (1S,4S)-2-Methyl-2,5-diazabicyclo[2.2.1]heptane.2HBr (24.8 g, 90.5 mmol), 2-fluoro-5-nitrotoluene (12.0 g, 77.3 mmol) and K2CO3 (43.7 g, 316.9 mmol) in 90 mL NMP were heated at 110° C. for 14 h by stirring. The reaction mixture was allowed to cool and quenched by pouring into water (500 mL). The contents were then stirred until precipitation was observed (3-4 h). The yellow solid formed was collected by filtration. The resulting filter cake washed with water (700 mL) and dried under vacuum suction. The filter cake was re-suspended in 10% EtOAc/hexanes (100 mL) as a slurry and then filtered to provide the desired material 2-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]-5-nitrotoluene (14.2 g, 74% based on nitrotoluene; 63% based on diazabicycloheptane) after drying; 1H NMR (DMSO-d6): δ 7.88-7.55 (m, 2H), 6.69 (d, 1H, J=8.8 Hz), 4.37 (s, 1H), 3.64 (dd, 1H, J=2.0 and 9.9 Hz), 3.38-3.55 (m, 2H), 2.81 (d, 1H, J=9.9 Hz), 2.65 (d, 1H, J=9.9 Hz), 2.33 (s, 3H), 2.23 (s, 3H), 1.87 (d, 1H, J=9.3 Hz), 1.75 (d, 1H, J=9.3 Hz). LCMS: purity: 98%; MS (m/e): 248 (MH+).

Workup

  1. temperatureto cool
  2. customquenched
  3. additionby pouring into water (500 mL)
  4. stirringThe contents were then stirred until precipitation
  5. custom(3-4 h)
  6. customThe yellow solid formed
  7. filtrationwas collected by filtration
  8. filtrationThe resulting filter cake
  9. washwashed with water (700 mL)
  10. customdried under vacuum suction
  11. filtrationfiltered

Sources & evidence

ORD record
ord-2cdbabd8d69240589005fa2a9610374c
Source dataset
uspto-grants-2014_05
Patent number
US08735418B2

Reaction notes

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