반응 #7769

반응 방정식

K2CO3

allyl bromide

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

DMF

EtOAc

→

title compound

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

용매

water

반응 조건

후처리

1. 1
   workup.ADDITIONwere added
2. 2
   세척The organic layer was washed with brine
3. 3
   기타dried
4. 4
   여과filtered
5. 5
   농축concentrated (2.05 g)
6. 6
   workup.DISSOLUTIONThe resulting material was dissolved in CH2Cl2 (4 mL)
7. 7
   농축the 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
    농축the 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
    세척was washed with brine solution and 1N HCl
15. 15
    건조The organic layer was dried (MgSO4)
16. 16
    여과filtered
17. 17
    농축concentrated 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
    세척was washed 1N HCl
23. 23
    건조The organic layer was dried (MgSO4)
24. 24
    여과filtered
25. 25
    농축concentrated

실험 절차

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).

출처