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

HRID 1875688Notes

Reaction equation

HRID 1875688 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 81.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

(1S,4S)-2-Methyl-2,5-diazabicyclo[2.2.1]heptane.2HBr (6 g, 21.89 mmol) (which can be prepared by similar methods as described in Braish, T. F et al., J. Org. Chem. (1990), Vol. 55, pp. 1684-1687), 2-fluoro-5-nitrotoluene (2.61 g, 16.82 mmol) and K2CO3 (10.57 g, 76.46 mmol) in 30 mL NMP were heated at 110° C. for 14 h while stirring. The reaction mixture was cooled to ambient temperature, poured onto ice-water and stirred until precipitate formation. The yellow solid formed was collected by filtration and washed with 15% EtOAc/hexanes to provide 2-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-nitrotoluene (3.4 g, 79%) in 98% purity; 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. additionpoured onto ice-water
  2. stirringstirred until precipitate formation
  3. customThe yellow solid formed
  4. filtrationwas collected by filtration
  5. washwashed with 15% EtOAc/hexanes

Sources & evidence

ORD record
ord-d467aa341a5345079849167914f10e80
Source dataset
uspto-grants-2012_11
Patent number
US08309566B2

Reaction notes

Loading…