Reaction #218408

Reaction equation

4-trifluoromethoxy-benzylamine

4-(2,5-difluoro-4-nitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

potassium carbonate

→

4-[2-fluoro-4-nitro-5-(4-trifluoromethoxy-benzylamino)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

Yield 80.3%

Solvents

DMF

DMF

dichloromethane

water

Conditions

Workup

1. 1
   workup.STIRRINGThe reaction mixture was then stirred for 48 h at rt
2. 2
   OtherAfter separation
3. 3
   Washthe organic phase was washed with brine (500 ml)
4. 4
   DryingThe combined organic phases were dried over magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated in vacuo
7. 7
   workup.STIRRINGThe solid residue was stirred with 150 ml heptane/ethylacetate 4:1
8. 8
   workup.ADDITIONAfter 10 minutes the suspension was diluted with 100 ml heptane
9. 9
   workup.STIRRINGafter additional 10 min stirring
10. 10
    Filtrationfiltered
11. 11
    OtherAfter drying in vacuo

Procedure

8 g of 4-(2,5-difluoro-4-nitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (23 mmol) and 3.82 g potassium carbonate (27.65 mmol) were suspended in 80 ml DMF under stirring and then treated dropwise within 10 min with a solution of 5.29 g of 4-trifluoromethoxy-benzylamine (27.65 mmol) in 30 ml DMF. The reaction mixture was then stirred for 48 h at rt, diluted with 500 ml dichloromethane and 1 liter of water. After separation, the organic phase was washed with brine (500 ml). The two aqueous phases were then reextracted with 2×250 ml dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated in vacuo. The solid residue was stirred with 150 ml heptane/ethylacetate 4:1. After 10 minutes the suspension was diluted with 100 ml heptane, and after additional 10 min stirring, filtered. After drying in vacuo, 9.5 g of 4-[2-fluoro-4-nitro-5-(4-trifluoromethoxy-benzylamino)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester was obtained as a yellow solid (80%). MS(ISP): 515.3 (M+H)+.

Source