Potassium Carbonate → HCID 68465699, compound

HRID 131226Notes

Reaction equation

HRID 131226 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18](F)[C:17]([N+:21]([O-:23])=[O:22])=[CH:16][C:15]=2[F:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[F:31][C:32]([F:43])([F:42])[O:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH2:39])=[CH:36][CH:35]=1>CN(C=O)C.ClCCl.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([NH:39][CH2:38][C:37]3[CH:40]=[CH:41][C:34]([O:33][C:32]([F:31])([F:42])[F:43])=[CH:35][CH:36]=3)[C:17]([N+:21]([O-:23])=[O:22])=[CH:16][C:15]=2[F:24])[CH2:10][CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 5718464-(Trifluoromethoxy)benzylamineHCID 66712179HCID 66712179, compound

Product 1

HCID 68465699HCID 68465699, compoundYield 80.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

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)+.

Workup

  1. stirringThe reaction mixture was then stirred for 48 h at rt
  2. customAfter separation
  3. washthe organic phase was washed with brine (500 ml)
  4. dry with materialThe combined organic phases were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. stirringThe solid residue was stirred with 150 ml heptane/ethylacetate 4:1
  8. additionAfter 10 minutes the suspension was diluted with 100 ml heptane
  9. stirringafter additional 10 min stirring
  10. filtrationfiltered
  11. customAfter drying in vacuo

Sources & evidence

ORD record
ord-f932251f261f4026a334df9d14d9d324
Source dataset
uspto-grants-2008_06
Patent number
US07384945B2

Reaction notes

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