Ethylenediamine → 2-(4-Bromo-3-methylphenyl)pyrazine

A stirred solution of (4-bromo-3-methylbenzoyl)methyl phenyl sulphone (D42, 1.5 g, 0.0044 mole) in dichloromethane (30 ml) at 0° C. under argon was treated with trifluoroacetic acid (0.70 ml, 0.005 mole) followed by trifluoroacetic anhydride (0.77 ml, 0.010 mole). After 30 minutes the solution was concentrated in vacuo, and the residue treated with a solution of sodium hydrogen carbonate (1.47 g, 0.017 mole) in water (30 ml), followed by ethanol (50 ml) and dichloromethane (50 ml). After 30 minutes, the two phase system was treated with ethylenediamine (0.33 ml, 0.005 mole) and stirred well at room temp. for 18 h, then the dichloromethane layer was separated, dried and concentrated in vacuo. The residue was dissolved in ethanol (30 ml) treated with potassium hydroxide (0.28 g, 0.005 mole) and heated under reflux for 6 h, then concentrated under vacuum and the residue treated with water (30 ml) and extracted with dichloromethane (2×50 ml). The combined extract was dried (Na2 SO4), concentrated in vacuo and the residue chromatographed on silica gel eluting with 25-40% ether/60-80 petrol to afford the title compound as a yellow solid (300 mg, 27%).

1. concentrationAfter 30 minutes the solution was concentrated in vacuo
2. customthe dichloromethane layer was separated
3. customdried
4. concentrationconcentrated in vacuo
5. dissolutionThe residue was dissolved in ethanol (30 ml)
6. temperatureheated
7. temperatureunder reflux for 6 h
8. concentrationconcentrated under vacuum
9. additionthe residue treated with water (30 ml)
10. extractionextracted with dichloromethane (2×50 ml)
11. extractionThe combined extract
12. customwas dried (Na2 SO4)
13. concentrationconcentrated in vacuo
14. customthe residue chromatographed on silica gel eluting with 25-40% ether/60-80 petrol

ORD record

ord-2aad943480e04696897b396c719f684a

Source dataset

uspto-grants-1998_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05801170