反应详情

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+).

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