Reaction #7769

Reaction equation

K2CO3

allyl bromide

2-(tert-Butoxycarbonyl)amino-5-trifluoromethylbenzoic acid

DMF

EtOAc

→

title compound

2-(3-Isopropyl-ureido)-5-trifluoromethyl-benzoic acid

Solvents

water

Conditions

Workup

1. 1
   workup.ADDITIONwere added
2. 2
   WashThe organic layer was washed with brine
3. 3
   Otherdried
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated (2.05 g)
6. 6
   workup.DISSOLUTIONThe resulting material was dissolved in CH2Cl2 (4 mL)
7. 7
   Concentrationthe solution was concentrated
8. 8
   workup.DISSOLUTIONThis material was dissolved in THF
9. 9
   workup.ADDITIONadded dropwise to a THF (50 mL) solution of trichloromethyl chloroformate (1.9 mL)
10. 10
    Concentrationthe solution was concentrated
11. 11
    workup.ADDITIONa THF (30 mL) solution of iso-propylamine (4.3 mL) was added
12. 12
    workup.WAITAfter 18 h
13. 13
    workup.ADDITIONthe solution was diluted with EtOAc
14. 14
    Washwas washed with brine solution and 1N HCl
15. 15
    DryingThe organic layer was dried (MgSO4)
16. 16
    Filtrationfiltered
17. 17
    Concentrationconcentrated to a white solid
18. 18
    workup.DISSOLUTIONThis solid was dissolved in CH3CN (22 mL)
19. 19
    workup.ADDITIONto the addition of pyrrolidine (0.41 mL) and Pd(PPh)4 (105 mg)
20. 20
    workup.WAITAfter 18 h
21. 21
    workup.ADDITIONthe solution was diluted with EtOAc
22. 22
    Washwas washed 1N HCl
23. 23
    DryingThe organic layer was dried (MgSO4)
24. 24
    Filtrationfiltered
25. 25
    Concentrationconcentrated

Procedure

2-(tert-Butoxycarbonyl)amino-5-trifluoromethylbenzoic acid (2 g) was dissolved in DMF prior to the addition of K2CO3 (1.08 g) and allyl bromide (0.68 mL). The mixture was stirred for 18 h before EtOAc and water were added. The organic layer was washed with brine, dried, filtered, and concentrated (2.05 g). The resulting material was dissolved in CH2Cl2 (4 mL) and TFA (4 mL). After 1 h, the solution was concentrated. This material was dissolved in THF and added dropwise to a THF (50 mL) solution of trichloromethyl chloroformate (1.9 mL). After stirring for 18 h, the solution was concentrated and a THF (30 mL) solution of iso-propylamine (4.3 mL) was added. After 18 h, the solution was diluted with EtOAc and was washed with brine solution and 1N HCl. The organic layer was dried (MgSO4), filtered, and concentrated to a white solid. This solid was dissolved in CH3CN (22 mL) prior to the addition of pyrrolidine (0.41 mL) and Pd(PPh)4 (105 mg). After 18 h, the solution was diluted with EtOAc and was washed 1N HCl. The organic layer was dried (MgSO4), filtered, and concentrated to give the title compound (1.1 g) as a white solid: 1H NMR (DMSO, δ ppm, 300 mHz) 1.11 (d, 6H), 3.78 (m, 1H), 7.63 (br d, 1H), 7.81 (dd, 1H), 8.14 (d, 1H), 8.64 (d, 1H), 10.27 (s, 1H), 13.83 (br s, 1H).

Source