Benzene, 1-fluoro-2-methyl-4-nitro- → 2-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-nitrotoluene

HRID 1027975Notes

Reaction equation

HRID 1027975 reaction equation
Br.Br.[CH3:3][N:4]1[CH2:9][C@@H:8]2[CH2:10][C@H:5]1[CH2:6][NH:7]2.F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[CH3:21].CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[CH3:3][N:4]1[CH2:9][C@@H:8]2[CH2:10][C@H:5]1[CH2:6][N:7]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 68001Benzene, 1-fluoro-2-methyl-4-nitro-HCID 81531DiisopropylethylamineHCID 15629279(1S)-2-methyl-2,5-diazobicyclo[2.2.1]heptane dihydrobromide

Product 1

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

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Alternatively, a heterogeneous mixture of (1S,4S)-2-methyl-2,5-diazabicyclo[2.2.1]heptane 2HBr salt (0.544 g, 2 mmol), 2-fluoro-5-nitrotoluene (0.310 g, 2 mmol) and DIPEA (0.387 g, 6 mmol) in NMP was refluxed for 2 days. The resulting residue was purified by column chromatography (silica gel, hexanes then 5-10% EtOAc in hexanes to afford 2-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-nitrotoluene, which was reduced by hydrogenation (H2, 10% Pd/C, MeOH, 40 PSI) to afford 3-methyl-4-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]aniline; LCMS: purity: 91%; MS (m/e): 218 (MH+).

Workup

  1. temperaturewas refluxed for 2 days
  2. customThe resulting residue was purified by column chromatography (silica gel, hexanes

Sources & evidence

ORD record
ord-939c2d07b4134722b45610e3e958aefa
Source dataset
uspto-grants-2014_05
Patent number
US08735418B2

Reaction notes

Loading…