Reaction #1340586

Reaction equation

2,6-dibromo-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-phenylamine

3-nitro-4-(1H-1,2,4-triazol-1-yl)benzoic acid

3-nitro-4-(1H-1,2,4-triazol-1-yl)benzoic acid

triethylamine

triethylamine

→

N-[2,6-dibromo-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-3-nitro-4-(1,2,4-triazol-1-yl)benzamide

Yield 65.0%

Solvents

1,2-dichloroethane

Conditions

Workup

1. 1
   Temperatureat reflux for 16 hours
2. 2
   workup.ADDITIONwere added over the course of 48 hours
3. 3
   OtherThe reaction was quenched by addition of aqueous hydrochloric acid (1M)
4. 4
   Otherthe phases were separated
5. 5
   WashThe organic phase was washed with saturated aqueous sodium hydrogen carbonate
6. 6
   Dryingdried over sodium sulfate
7. 7
   Concentrationconcentrated
8. 8
   OtherThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1:2)
9. 9
   Otherto give Compound No

Procedure

To a suspension of 2,6-dibromo-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-phenylamine (Example I1) (635 mg, 1.35 mmol) in 1,2-dichloroethane (6.5 ml) was added triethylamine (0.57 ml, 4.06 mmol), followed by 3-nitro-4-(1H-1,2,4-triazol-1-yl)benzoic acid (634 mg, 2.7 mmol) and bis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP—Cl”) (689 mg, 2.7 mmol). The reaction mixture was stirred at reflux for 16 hours. The progress of the reaction was followed by thin layer chromatography and, because it was necessary in this case, further doses of 3-nitro-4-(1H-1,2,4-triazol-1-yl)benzoic acid (4×0.675 mmol), bis(2-oxo-3-oxazolidinyl)phosphonic chloride (4×1.35 mmol) and triethylamine (4×1.35 mmol) were added over the course of 48 hours. The reaction was quenched by addition of aqueous hydrochloric acid (1M) and the phases were separated. The organic phase was washed with saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1:2) to give Compound No. A4 of Table A (605 mg, 65% yield).

Source