1-(3-Chlorophenyl)ethanone → cis-1-[3-(3,5-Dimethyl-piperazin-1-yl)-phenyl]-ethanone

HRID 885853Notes

Reaction equation

HRID 885853 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.Cl[C:38]1[CH:39]=[C:40]([C:44](=[O:46])[CH3:45])[CH:41]=[CH:42][CH:43]=1.[CH3:47][C@@H:48]1[CH2:53][NH:52][CH2:51][C@H:50]([CH3:54])[NH:49]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].COCCOC>[CH3:47][C@H:48]1[NH:49][C@@H:50]([CH3:54])[CH2:51][N:52]([C:38]2[CH:39]=[C:40]([C:44](=[O:46])[CH3:45])[CH:41]=[CH:42][CH:43]=2)[CH2:53]1

Participants

7

Reactant 4

HCID 149331-(3-Chlorophenyl)ethanoneHCID 62657Potassium Phosphate, TribasicHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl2×HCID 6950261rel-(2R,6S)-2,6-dimethylpiperazine

Product 1

HCID 67049822cis-1-[3-(3,5-Dimethyl-piperazin-1-yl)-phenyl]-ethanoneYield 15%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

An oven-dried MW tube was charged with Pd2(dba)3 (592 mg, 0.65 mmol), K3PO4 (1.92 g, 9.06 mmol) and (2′-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethyl-amine (127 mg, 0.32 mmol). The tube was purged and backfilled with N2 and then 1-(3-chloro-phenyl)-ethanone (1 g, 6.47 mmol), (2R,6S)-2,6-dimethyl-piperazine (886 mg, 7.76 mmol) and DME (10 ml) were added. The mixture was heated in a MW apparatus for 4 h at 100° C. and then further Pd2(dba)3 (592 mg, 0.65 mmol) and (2′-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethyl-amine (127 mg, 0.32 mmol) were added. The reaction mixture was heated to 100° C. for additional 10 h and then the solid was filtered off over a Celite pad. The filtrate was diluted with AcOEt and extracted with 1 M HCl. The aqueous phase was brought to basic conditions with NH4OH and extracted with AcOEt. The organic phase was dried over Na2SO4 and evaporated in vacuo. The crude reaction mixture was purified by column chromatography (eluent: AcOEt/MeOH 8:2) to give 226 mg of 1-[3-((3R,5S)-3,5-dimethyl-piperazin-1-yl)-phenyl]-ethanone.

Workup

  1. customThe tube was purged
  2. temperatureThe reaction mixture was heated to 100° C. for additional 10 h
  3. filtrationthe solid was filtered off over a Celite pad
  4. additionThe filtrate was diluted with AcOEt
  5. extractionextracted with 1 M HCl
  6. extractionextracted with AcOEt
  7. dry with materialThe organic phase was dried over Na2SO4
  8. customevaporated in vacuo
  9. customThe crude reaction mixture
  10. customwas purified by column chromatography (eluent: AcOEt/MeOH 8:2)

Sources & evidence

ORD record
ord-0c68304cf3754641a341323b02e2bcfd
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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