tert-Butyl piperazine-1-carboxylate → tert-Butyl 4-(4-fluoro-2-(trifluoromethyl)-phenyl)piperazine-1-carboxylate

HRID 1868077Notes

Reaction equation

HRID 1868077 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[C:22]([F:25])([F:24])[F:23].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C(OC(=O)C)C.C1(C)C=CC=CC=1>[C:10]([O:9][C:7]([N:1]1[CH2:6][CH2:5][N:4]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[C:22]([F:23])([F:25])[F:24])[CH2:3][CH2:2]1)=[O:8])([CH3:13])([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 5209832-Bromo-5-fluorobenzotrifluorideHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxide

Product 1

HCID 57979766tert-Butyl 4-(4-fluoro-2-(trifluoromethyl)-phenyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl piperazine-1-carboxylate 1.04 g, (5.6 mmol), 2-bromo-5-fluoro benzotrifluoride (1.21 g, 5.0 mmol), tris(dibenzylidineacetone)dipalladium (0) (45.8 mg, 0.05 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (93.4 mg, 0.15 mmol) and sodium tert-butoxide (600 mg, 6.25 mmol) were charged to a microwave vial. Toluene (10.0 mL) was introduced under nitrogen atmosphere and the reaction mixture was irradiated at 110° C. for 30 minutes. Reaction was complete as determined by TLC. The reaction was repeated four times. Reaction mixtures were combined, diluted with ethylacetate, washed with water, saturated brine then dried over MgSO4 and concentrated. The crude product was purified via flash column chromatography to yield tert-butyl-4-(4-fluoro-2-(trifluoromethyl)phenyl)piperazine-1-carboxylate in quantitative yield (6.8 g) as yellow oil.

Workup

  1. additionwere charged to a microwave vial
  2. customthe reaction mixture was irradiated at 110° C. for 30 minutes
  3. customReaction
  4. customReaction mixtures
  5. washwashed with water, saturated brine
  6. dry with materialthen dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified via flash column chromatography

Sources & evidence

ORD record
ord-a8d356d734154f1d95b68dbc2fe36e54
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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