反应详情

温度

110 °C

1 g of 2-fluoro-5-trifluoromethyl-benzoic acid (4.81 mmol) was dissolved in DCM (10 ml) and 1.03 ml of oxalylchloride (12.01 mmol) and a drop of DMF were added at RT. The mixture was stirred for 1 h before all volatile materials were removed in vacuo. The remaining residue was again dissolved in DCM (10 ml) and 1.4 ml of ethanol was added. After 1 h the reaction mixture was diluted with DCM and then washed with 10% aqueous KHCO3 solution, water and brine, dried (MgSO4), filtered and concentrated. The remaining material was dissolved in DMSO (6 ml), 5.57 ml of cyclopropylamine (79.4 mmol) were added and the mixture was heated to 110° C. over night in a sealed tube. The reaction mixture was then cooled to RT, diluted with ethyl acetate, washed with diluted HCl, 10% aqueous KHCO3 solution, water and brine, dried (MgSO4), filtered and concentrated. Then THF (20 ml), methanol (10 ml) and 8 ml of a 1N LiOH solution were added and the resulting solution was stirred over night at RT. The organic solvents were then removed in vacuo and the solution was acidified with 1N HCl and extracted with ethyl acetate. The combined organic extracts were dried (MgSO4), filtered and concentrated. The remaining solid was triturated with a small amount of chloroform. Filtration gave 391 mg (33%) of the title compound as light brown crystals. 1HNMR (DMSO-d6, 300 MHz): δ 0.53 (m, 2H), 0.85 (m, 2H), 2.56 (m, 1H), 7.24 (d, J=8.9 Hz, 1H), 7.71 (dd, J=8.9 and 2.1 Hz, 1H), 8.02 (s, 1H), 8.30 (br s, 1H), 13.21 (br s, 1H).

1. customwere removed in vacuo
2. dissolutionThe remaining residue was again dissolved in DCM (10 ml)
3. addition1.4 ml of ethanol was added
4. additionAfter 1 h the reaction mixture was diluted with DCM
5. washwashed with 10% aqueous KHCO3 solution, water and brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. dissolutionThe remaining material was dissolved in DMSO (6 ml)
10. temperatureThe reaction mixture was then cooled to RT
11. washwashed with diluted HCl, 10% aqueous KHCO3 solution, water and brine
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated
15. additionThen THF (20 ml), methanol (10 ml) and 8 ml of a 1N LiOH solution were added
16. stirringthe resulting solution was stirred over night at RT
17. customThe organic solvents were then removed in vacuo
18. extractionextracted with ethyl acetate
19. dry with materialThe combined organic extracts were dried (MgSO4)
20. filtrationfiltered
21. concentrationconcentrated
22. customThe remaining solid was triturated with a small amount of chloroform
23. filtrationFiltration