2-Amino-4-(trifluoromethyl)phenol → N-(4-Bromo-2-fluorophenyl)-5-(trifluoromethyl)-1,3-benzoxazol-2-amine

HRID 30906Notes

Reaction equation

HRID 30906 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[OH:12].[Br:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]=[C:21]=S)=[C:16]([F:23])[CH:15]=1.Cl.CN(C)CCCN=C=NCC>C(O)C>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]2[O:12][C:3]3[CH:4]=[CH:5][C:6]([C:8]([F:9])([F:10])[F:11])=[CH:7][C:2]=3[N:1]=2)=[C:16]([F:23])[CH:15]=1

Participants

5

Reactant 3

HCID 1202462-Amino-4-(trifluoromethyl)phenolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27570034-Bromo-2-fluorophenylisothiocyanate

Product 1

HCID 23549343N-(4-Bromo-2-fluorophenyl)-5-(trifluoromethyl)-1,3-benzoxazol-2-amineYield 18%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-Amino-4-(trifluoromethyl)phenol (580 mg, 3.25 mmol) and 4-bromo-2-fluoro-1-isothio-cyanatobenzene (750 mg, 3.25 mmol) were stirred in ethyl alcohol at ambient temperature for 18 h. The flask was charged with 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDCI) (405 mg, 2.12 mmol), and the mixture was stirred for 2 h before being heated at reflux overnight. The reaction was allowed to cool to rt and was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with 2 N aqueous hydrochloric acid solution and water, dried (Na2SO4), and concentrated in vacuo. The crude material was suspended in ether, sonicated, and the resulting solid was collected by filtration to provide the title compound (214 mg, 18%). LC-MS m/z 375.1 (MH+), retention time 3.70 minutes.

Workup

  1. temperaturebefore being heated
  2. temperatureat reflux overnight
  3. concentrationwas concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with 2 N aqueous hydrochloric acid solution and water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customsonicated
  9. filtrationthe resulting solid was collected by filtration

Sources & evidence

ORD record
ord-bbd0f4f801c04a91ae85780ff3f1de61
Source dataset
uspto-grants-2008_09
Patent number
US07423156B2

Reaction notes

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