2-(Di-tert-butylphosphino)biphenyl → HCID 58834358, compound

HRID 1710662Notes

Reaction equation

HRID 1710662 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[NH:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]1)=[O:4].Br[C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([O:26][CH3:27])[CH:20]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3]([CH:5]1[N:10]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([O:26][CH3:27])[CH:20]=2)[CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]1)=[O:4]

Participants

7

Reactant 4

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 27568191-tert-Butyl 3-methyl piperazine-1,3-dicarboxylateHCID 27695675-Bromo-2-chloroanisoleHCID 23676156Sodium t-butoxide

Product 1

HCID 58834358HCID 58834358, compoundYield 15.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a vial containing piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (907 mg, 4.04 mmol), was added 4-bromo-1-chloro-2-methoxybenzene (913 mg, 4.12 mmol), palladium acetate (33 mg, 0.14 mmol) and 2-(di-tert-butylphosphino)biphenyl (88 mg, 0.29 mmol). The vial was evacuated and back-filled with nitrogen and to it was added toluene (2 mL). The reaction mixture was heated to 80° C. for 5 min to give a homogeneous solution. Upon cooling to room temperature, sodium tert-butoxide (557 mg, 5.80 mmol) was added to the reaction solution. The resultant mixture was again heated to 80° C. After 4 h, the reaction mixture was cooled to room temperature, then diluted with EtOAc (10 mL) and hexanes (10 mL). The resultant solution was filtered through celite, and the filtrate concentrated in vacuo and purified by silica gel flash chromatography (30 g) (20% EtOAc/Hexanes) to afford 4-(4-chloro-3-methoxyphenyl)piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (63) (239 mg, 15% yield): HPLC retention time=2.72 minutes. MS (ES) [M+H]+ expected 385.2, found 385.1.

Workup

  1. customThe vial was evacuated
  2. additionback-filled with nitrogen and to it
  3. additionwas added toluene (2 mL)
  4. customto give a homogeneous solution
  5. temperatureUpon cooling to room temperature
  6. temperaturethe reaction mixture was cooled to room temperature
  7. filtrationThe resultant solution was filtered through celite
  8. concentrationthe filtrate concentrated in vacuo
  9. custompurified by silica gel flash chromatography (30 g) (20% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-dd48000109304425bd8dc7c9fdc433f5
Source dataset
uspto-grants-2010_09
Patent number
US07790726B2

Reaction notes

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