tert-Butyl piperazine-1-carboxylate → HCID 59479286, compound

HRID 1373530Notes

Reaction equation

HRID 1373530 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1OS(C(F)(F)F)(=O)=O.[C:20]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:23]([O:22][C:20]([N:27]1[CH2:32][CH2:31][N:30]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([C:8]([F:11])([F:10])[F:9])[C:2]=2[Cl:1])[CH2:29][CH2:28]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 59479282HCID 59479282, compound

Product 1

HCID 59479286HCID 59479286, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

An intermediate, 1-(2-Chloro-3-trifluoromethyl-phenyl)-piperazine was produced as follows: To a stirred solution of trifluoro-methanesulfonic acid 2-chloro-3-trifluoromethyl-phenyl ester (5.0 g, 15.20 mmol) in toluene (50 mL) at room temperature, was added 1-boc-piperazine (3.39 g, 18.20 mmol), tris-(dibenzylideneacetone)di-palladium(0) (Pd2(dba)3) (3.49 g, 38.10 mmol), tert-2,2′-bis(diphenyl)phosphino-1,1′-binaphthyl (BINAP) (4.27 g, 68.60 mmol) and sodium tert-butoxide (2.04 g, 21.30 mmol). The mixture was degassed, filled with N2, degassed and heated at 80° C. for 1.5 h. The mixture was diluted with ethyl acetate, celite was added and the mixture was stirred at room temperature for 15 min. It was filtered through a pad of silica gel and the pad was washed with additional amounts of ethyl acetate, The combined solvent was removed in vacuo and the residue was purified on a silica gel column using hexanes-ethyl acetate (5:1) as eluent to give 4-(2-chloro-3-trifluoromethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (2.30 g, 42%) as an oil. 1H NMR (400 MHz, CDCl3): δ 7.35 (m, 2H), 7.22 (d, 1H), 3.62 (br s, 4H), 3.05 (br s, 4H), 1.55 (s, 9H).

Workup

  1. customThe mixture was degassed
  2. additionfilled with N2
  3. customdegassed
  4. additionThe mixture was diluted with ethyl acetate, celite
  5. additionwas added
  6. filtrationIt was filtered through a pad of silica gel
  7. washthe pad was washed with additional amounts of ethyl acetate
  8. customThe combined solvent was removed in vacuo
  9. customthe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-3509c62f01364f5985db2c362fd0e7cd
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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