1-(3-(Trifluoromethyl)phenyl)piperazine → 1,3-Dichloro-5-methoxy-2-{4-[3-(trifluoromethyl)phenyl]piperazinyl}benzene

HRID 2242516Notes

Reaction equation

HRID 2242516 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([Cl:10])[C:3]=1Br.[F:12][C:13]([F:27])([F:26])[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[CH:15]=1.C1(OP(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(OC2C=CC=CC=2)(OC2C=CC=CC=2)=O)(OC2C=CC=CC=2)=O)C=CC=CC=1.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]>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([Cl:10])[C:3]=1[N:23]1[CH2:22][CH2:21][N:20]([C:16]2[CH:17]=[CH:18][CH:19]=[C:14]([C:13]([F:26])([F:27])[F:12])[CH:15]=2)[CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 42961-(3-(Trifluoromethyl)phenyl)piperazineHCID 20142311HCID 20142311, compoundHCID 23676156Sodium t-butoxideHCID 592048362-Bromo-1,3-dichloro-5-methoxybenzene

Product 1

HCID 685431491,3-Dichloro-5-methoxy-2-{4-[3-(trifluoromethyl)phenyl]piperazinyl}benzeneYield 54%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A stirred mixture of 2.5 grams (0.0096 mole) of 1,3-dichloro-5-methoxy-2-bromobenzene (known compound), 0.18 mL (0.0096 mole) of 1-(α,α,α-trifluoro-meta-tolyl)piperazine (known compound), 0.18 gram (0.0002 mole) of tris(dibenzylideneacetone)dipalladium(0), 0.36 gram (0.0006 mole) of racemic-2,2′-bis(diphenylphosphono)-1,1′-binaphthyl, and 1.66 grams (0.017 mole) of sodium tert-butoxide in 100 mL of toluene was heated at 100° C. for about 60 hours. After this time, the reaction mixture was cooled and washed with two 10 mL portions of water. The organic layer was dried with sodium sulfate, filtered, and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using 1:3 and 1:1 mixtures of methylene chloride:hexane as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 2.1 grams of the subject compound, mp 87-89° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. temperatureAfter this time, the reaction mixture was cooled
  2. washwashed with two 10 mL portions of water
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure to a residue
  6. customThe residue was purified with column chromatography on silica gel using 1:3 and 1:1 mixtures of methylene chloride
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-090d8e08e8d744478dc5834bd2f3530a
Source dataset
uspto-grants-2010_03
Patent number
US07671201B2

Reaction notes

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