Iodobenzene → 2-Phenethyl-1,4-bis-(toluene-4-sulfonyl)-piperazine

HRID 1350381Notes

Reaction equation

HRID 1350381 reaction equation
B1[CH:6]2[CH2:7][CH2:8][CH2:9][CH:2]1CC[CH2:5]2.[C:10]1([CH3:37])[CH:15]=[CH:14][C:13]([S:16]([N:19]2[CH2:24][CH2:23][N:22]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[CH2:21][C@@H:20]2[CH:35]=[CH2:36])(=[O:18])=[O:17])=[CH:12][CH:11]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.IC1C=CC=CC=1.[OH-].[Na+]>C1COCC1.[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>[CH2:35]([CH:20]1[CH2:21][N:22]([S:25]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)(=[O:27])=[O:26])[CH2:23][CH2:24][N:19]1[S:16]([C:13]1[CH:14]=[CH:15][C:10]([CH3:37])=[CH:11][CH:12]=1)(=[O:17])=[O:18])[CH2:36][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:2]=1

Participants

8

Reactant 5

HCID 11575IodobenzeneHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 14612246(S)-1,4-bis(toluene-4-sulfonyl)-2-vinyl-piperazine

Product 1

HCID 694865562-Phenethyl-1,4-bis-(toluene-4-sulfonyl)-piperazineYield 75%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Add 9-BBN (0.5 M THF solution, 13.7 mL, 6.85 mmol) to a 100 mL schlenk flask containing (S)-1,4-bis(toluene-4-sulfonyl)-2-vinyl-piperazine(0.96 g, 2.3 mmol) in THF (5 mL), at room temperature under nitrogen and stir. After 18 hours, treat the reaction with tetrakis(triphenylphosphine) palladium (53 mg, 0.046 mmol), triphenyl phosphine (94.6 mg, 0.36 mmol), iodiobenzene (0.703 g, 3.4 mmol) and 3N NaOH (2.8 mL, 8.4 mmol) and heat to reflux. After 24 hours, cool the reaction to room temperature, remove in vacuo the THF solvent, dilute the residue with CH2Cl2, wash with 1N HCl, brine, and dry over Na2SO4. Purification by flash chromatography twice (Gradient: Hexanes/CH2Cl2=50/50, to Hexanes/CH2Cl2/EtOAc=40/40/10), and recrystallization in MeOH gives 860 mg (75%) of the title compound: mass spectrum (electrospray): (m/z)=499.2 (M+1); 1H NMR (CDCl3): δ7.58–7.54 (m, 4H), 7.33–7.20 (m, 7H), 7.19–7.07 (m, 2H), 3.99 (m, 1H), 3.81–3.78 (m, 1H), 3.64–3.60 (m, 2H), 3.22 (dt, 1H, J=3.2 Hz, J=12.4 Hz), 2.57–2.41 (m, 2H), 2.41 (s, 3H), 2.33 (s, 3H), 2.33–2.20 (m, 2H), 2.03–1.98 (m, 1H), 1.75–1.63 (m, 1H).

Workup

  1. additiontreat
  2. temperatureheat to reflux
  3. waitAfter 24 hours
  4. temperaturecool
  5. customthe reaction to room temperature
  6. customremove in vacuo the THF solvent
  7. additiondilute the residue with CH2Cl2
  8. washwash with 1N HCl, brine
  9. dry with materialdry over Na2SO4
  10. customPurification
  11. customby flash chromatography twice (Gradient: Hexanes/CH2Cl2=50/50, to Hexanes/CH2Cl2/EtOAc=40/40/10), and recrystallization in MeOH

Sources & evidence

ORD record
ord-a1f9ab8ea5f44ab892ea2e5898ea6d0a
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

Loading…