4-Bromo-2-chloro-alpha,alpha,alpha-trifluorotoluene → HCID 23149844, compound

HRID 1670771Notes

Reaction equation

HRID 1670771 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][NH:11][CH:10]([CH3:14])[CH2:9]1)=O)(C)(C)C.Br[C:16]1[CH:17]=[CH:18][C:19]([Cl:26])=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1.CC(C)([O-])C.[Na+]>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].C1(C)C=CC=CC=1>[ClH:26].[Cl:26][C:19]1[CH:18]=[CH:17][C:16]([N:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH:10]2[CH3:14])=[CH:21][C:20]=1[C:22]([F:23])([F:24])[F:25]

Participants

6

Reactant 3

HCID 679594-Bromo-2-chloro-alpha,alpha,alpha-trifluorotolueneHCID 2756810tert-Butyl 3-methylpiperazine-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 23149844HCID 23149844, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

1-(tert-Butoxycarbonyl)-3-methylpiperazine (Oakwood Co., 1.36 g), 5-bromo-2-chlorobenzotrifluoride (Tokyo Chemical Industry CO., LTD., 2.0 g), 2-(di-tert-phosphino)biphenyl (STREM, 41 mg), tris(dibenzylideneacetone)dipalladium (Aldrich Co., 62 mg) and sodium tert-butoxide (980 mg) were added to toluene (10 ml), and the mixture was stirred with heating at 60° C. for 3 hr. After completion of the reaction, the insoluble material was filtered off, and the filtrate was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (7:1-3:1)). A 4N hydrochloric acid-ethyl acetate solution was added to the obtained solid and the mixture was stirred for 5 hr. Diethyl ether was added thereto, and the precipitated solid was collected by filtration to give 1-[4-chloro-3-(trifluoromethyl)phenyl]-2-methylpiperazine hydrochloride (692 mg, yield 32%).

Workup

  1. customAfter completion of the reaction
  2. filtrationthe insoluble material was filtered off
  3. customthe filtrate was evaporated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (7:1-3:1))
  5. additionA 4N hydrochloric acid-ethyl acetate solution was added to the obtained solid
  6. stirringthe mixture was stirred for 5 hr
  7. additionDiethyl ether was added
  8. filtrationthe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-458da612083c45c19afb824a572917d6
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Reaction notes

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