Cesium carbonate → HCID 69420920, compound

HRID 1373531Notes

Reaction equation

HRID 1373531 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[O:9][CH3:10].[C:11]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>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].CCOCC.CCOC(C)=O>[C:14]([O:13][C:11]([N:18]1[CH2:23][CH2:22][N:21]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=2[O:9][CH3:10])[CH2:20][CH2:19]1)=[O:12])([CH3:17])([CH3:15])[CH3:16]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 161272,6-DichloroanisoleHCID 143452tert-Butyl piperazine-1-carboxylate2×HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl

Product 1

HCID 69420920HCID 69420920, compoundYield 8%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

An intermediate compound 1-(3-Chloro-2-methoxy-phenyl)-piperazine, was produced as follows. A solution of 2,6-dichloroanisole (1.55 mL, 11.30 mmol) in dry toluene (40 mL) was degassed for 10 min by blowing nitrogen into the solution. This solution was then added via cannula to a flask containing Boc-piperazine 3.16 g, 16.90 mmol), Cs2CO3 (5.15 g, 15.80 mmol), Pd2(dba)3 (414 mg, 0.452 mmol, 4 mol %) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (356 mg, 0.904 mmol, 8 mol %) under nitrogen. The reaction mixture was heated at 100° C. overnight (16 h). MS showed a small product peak and a large Boc-piperazine peak. TLC (10% EtOAc/Hex) showed a product spot. The reaction was allowed to cool to room temperature and Et2O was added. The mixture was filtered through Celite washing with Et2O. The filtrate was washed 3 times with 0.5 M citric acid (to remove excess Boc-piperazine) and once with brine, dried over MgSO4 and concentrated to give a brown oil. Purification by SiO2 chromatography (10% EtOAC/Hexanes) gave 4-(3-chloro-2-methoxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester as a pale yellow solid (278 mg, 8%).

Workup

  1. additionThis solution was then added via cannula to a flask
  2. temperatureto cool to room temperature
  3. filtrationThe mixture was filtered through Celite
  4. washwashing with Et2O
  5. washThe filtrate was washed 3 times with 0.5 M citric acid (to remove excess Boc-piperazine)
  6. dry with materialonce with brine, dried over MgSO4
  7. concentrationconcentrated
  8. customto give a brown oil
  9. customPurification by SiO2 chromatography (10% EtOAC/Hexanes)

Sources & evidence

ORD record
ord-8ee1243287974c00b1cb1d38387cb035
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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