反応 #7769

反応方程式

K2CO3

allyl bromide

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

DMF

EtOAc

→

title compound

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

溶媒

water

反応条件

後処理

1. 1
   workup.ADDITIONwere added
2. 2
   洗浄The organic layer was washed with brine
3. 3
   その他dried
4. 4
   ろ過filtered
5. 5
   濃縮concentrated (2.05 g)
6. 6
   workup.DISSOLUTIONThe resulting material was dissolved in CH2Cl2 (4 mL)
7. 7
   濃縮the 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
    濃縮the 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
    洗浄was washed with brine solution and 1N HCl
15. 15
    乾燥The organic layer was dried (MgSO4)
16. 16
    ろ過filtered
17. 17
    濃縮concentrated 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
    洗浄was washed 1N HCl
23. 23
    乾燥The organic layer was dried (MgSO4)
24. 24
    ろ過filtered
25. 25
    濃縮concentrated

実験手順

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).

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