Iodobenzene → (S)-1,4-dibenzyl-2-phenethyl-piperazine

HRID 1350383Notes

Reaction equation

HRID 1350383 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@@H:9]1[CH:21]=[CH2:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:23]12B[CH:27]([CH2:28][CH2:29][CH2:30]1)[CH2:26]CC2.IC1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[Na+]>C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@@H:9]1[CH2:21][CH2:22][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:23]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 11575IodobenzeneHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 17759473(S)-1,4-dibenzyl-2-vinylpiperazine

Product 1

HCID 69486804(S)-1,4-dibenzyl-2-phenethyl-piperazineYield 84%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Combine (S)-1,4-dibenzyl-2-vinyl-piperazine (4.9 g, 16.63 mmol) and 9-borabicyclo[3.3.1]nonane (199.6 ml, 99.78 mmol, 0.5 M in THF) and stir at ambient temperature. After 24 hours, add iodo-benzene (5.1 g, 24.95 mmol), triphenylphosphine (697.9 mg, 2.66 mmol), tetrakis(triphenylphosphine) palladium(0)(384.3 mg, 0.33 mmol), and 3N NaOH (13.7 mL) and stir at 60° C. After 22 hours, dilute the mixture with ethyl acetate and wash it with 1N sulfuric acid. Adjust the pH to 14, extract with ethyl acetate, and combine, wash (brine), dry (sodium sulfate), and reduce the extracts to residue. Purify the residue on silica gel using a ethyl acetate/hexanes gradient (5:95 to 10:90) to give (5.15 g, 84%) of the title compound as a white solid: mp 86–90° C.; mass spectrum (ion spray): m/z=371.3 (M+1).

Workup

  1. waitAfter 22 hours
  2. washwash it with 1N sulfuric acid
  3. extractionextract with ethyl acetate
  4. washwash (brine)
  5. dry with materialdry (sodium sulfate)
  6. customPurify the residue on silica gel using a ethyl acetate/hexanes gradient (5:95 to 10:90)

Sources & evidence

ORD record
ord-54a7b9f8ad704506a0a78d9c90ef688e
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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