Dimethylformamide → 2-(3-Isopropyl-ureido)-5-trifluoromethyl-benzoic Acid

HRID 7673Notes

Reaction equation

HRID 7673 reaction equation
C(O[C:6]([NH:8][C:9]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:10]=1[C:11]([OH:13])=[O:12])=[O:7])(C)(C)C.C([O-])([O-])=O.[K+].[K+].[CH2:28](Br)[CH:29]=[CH2:30].CCOC(C)=O.C[N:39](C=O)C>O>[CH:29]([NH:39][C:6](=[O:7])[NH:8][C:9]1[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][C:10]=1[C:11]([OH:13])=[O:12])([CH3:30])[CH3:28]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 7841Allyl bromideHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 150338862-((tert-Butoxycarbonyl)amino)-5-(trifluoromethyl)benzoic acid

Product 1

HCID 219911512-(3-Isopropyl-ureido)-5-trifluoromethyl-benzoic Acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

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).

Workup

  1. additionwere added
  2. washThe organic layer was washed with brine
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated (2.05 g)
  6. dissolutionThe resulting material was dissolved in CH2Cl2 (4 mL)
  7. concentrationthe solution was concentrated
  8. dissolutionThis material was dissolved in THF
  9. additionadded dropwise to a THF (50 mL) solution of trichloromethyl chloroformate (1.9 mL)
  10. concentrationthe solution was concentrated
  11. additiona THF (30 mL) solution of iso-propylamine (4.3 mL) was added
  12. waitAfter 18 h
  13. additionthe solution was diluted with EtOAc
  14. washwas washed with brine solution and 1N HCl
  15. dry with materialThe organic layer was dried (MgSO4)
  16. filtrationfiltered
  17. concentrationconcentrated to a white solid
  18. dissolutionThis solid was dissolved in CH3CN (22 mL)
  19. additionto the addition of pyrrolidine (0.41 mL) and Pd(PPh)4 (105 mg)
  20. waitAfter 18 h
  21. additionthe solution was diluted with EtOAc
  22. washwas washed 1N HCl
  23. dry with materialThe organic layer was dried (MgSO4)
  24. filtrationfiltered
  25. concentrationconcentrated

Sources & evidence

ORD record
ord-49117191fe304ac4a8e3e2f12b232b4f
Source dataset
uspto-grants-2006_08
Patent number
US07087604B2

Reaction notes

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