Binap, (A+-)- → HCID 67183231, compound

HRID 1798745Notes

Reaction equation

HRID 1798745 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:10])=[C:6]([O:8][CH3:9])[CH:7]=1.[CH3:11][C:12]1([CH3:18])[CH2:17][NH:16][CH2:15][CH2:14][NH:13]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)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].CCOC(C)=O>[ClH:10].[ClH:10].[Cl:10][C:5]1[CH:4]=[CH:3][C:2]([N:13]2[CH2:14][CH2:15][NH:16][CH2:17][C:12]2([CH3:18])[CH3:11])=[CH:7][C:6]=1[O:8][CH3:9]

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 27695675-Bromo-2-chloroanisoleHCID 146641862,2-DimethylpiperazineHCID 23676156Sodium t-butoxide

Product 1

HCID 67183231HCID 67183231, compoundYield 219.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
60 °C

Procedure

A mixture of 5-bromo-2-chloroanisole (3.70 g, 16.7 mmol, 1 equiv), 2,2-dimethyl-piperazine (2.2 g, 1.2 equiv) and rac-BINAP (1.04 g, 0.1 equiv) in toluene (35 mL) was degassed with compressed nitrogen for 5 min. To the mixture were added NaOt-Bu (2.3 g, 1.4 equiv) and Pd2(dba)3 (54 mg, 0.005 equiv). The resulting mixture was heated at 60° C. overnight and cooled to room temperature. EtOAc (˜200 mL) was added and the mixture was filtered through celite. The filtrate was washed with saturated aqueous K2CO3 (200 mL), saturated aqueous NaHCO3 (200 mL), and brine (200 mL) sequentially and then dried over magnesium sulfate. The resulting residue after evaporation was dissolved in EtOAc (100 mL) and treated with 2 N HCl in Et2O (100 mL) at room temperature for 2 h. A solid was collected by filtration and dried in vacuo to afford 4-(4-chloro-3-methoxy-phenyl)-3,3-dimethylpiperazine dihydrochloride (4.0 g). MS (ES) m/z 255.1 (M+H+).

Workup

  1. customwas degassed with compressed nitrogen for 5 min
  2. temperaturecooled to room temperature
  3. filtrationthe mixture was filtered through celite
  4. washThe filtrate was washed with saturated aqueous K2CO3 (200 mL), saturated aqueous NaHCO3 (200 mL), and brine (200 mL) sequentially
  5. dry with materialdried over magnesium sulfate
  6. customThe resulting residue after evaporation
  7. dissolutionwas dissolved in EtOAc (100 mL)
  8. additiontreated with 2 N HCl in Et2O (100 mL) at room temperature for 2 h
  9. filtrationA solid was collected by filtration
  10. customdried in vacuo

Sources & evidence

ORD record
ord-f124846826754255897819e7fabbd083
Source dataset
uspto-grants-2013_01
Patent number
US08343975B2

Reaction notes

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