2,5-Dibromopyridine → 1-(5-Bromo-2-pyridinyl)-4-(phenylsulfonyl)piperazine

HRID 1972367Notes

Reaction equation

HRID 1972367 reaction equation
Cl.[C:2]1([S:8]([N:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)(=[O:10])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][N:19]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O.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].CO.C1(C)C=CC=CC=1>[Br:24][C:21]1[CH:22]=[CH:23][C:18]([N:14]2[CH2:15][CH2:16][N:11]([S:8]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)(=[O:10])=[O:9])[CH2:12][CH2:13]2)=[N:19][CH:20]=1

Participants

9

Reactant 4

HCID 693532,5-DibromopyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27565811-(Benzenesulfonyl)piperazine hydrochlorideHCID 23676156Sodium t-butoxide

Product 1

HCID 375348861-(5-Bromo-2-pyridinyl)-4-(phenylsulfonyl)piperazineYield 43.8%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A 350 ml, pressure vessel was charged with 4-(phenylsulfonyl)piperazine hydrochloride (1.50 g, 5.71 mmol, Example 15, step 1), 2,5-dibromopyridine (1.76 g, 7.42 mmol, Sigma-Aldrich, St. Louis, Mo.), 100 mL of toluene, sodium tert-butoxide (1.37 g, 14.3 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.105 g, 0.114 mmol, Strem Chemical Inc, Newburyport, Mass.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos) (0.198 g, 0.343 mmol, Strem Chemical Inc, Newburyport, Mass.). The tube was sealed and heated at 110° C. for 3 h. After that time, the reaction was cooled to room temperature, diluted with water (20 mL) and extracted with EtOAc (2×50 mL). The organic layer was separated, dried (MgSO4) and concentrated to give a yellow solid. This solid was slurried with cold (0° C.) MeOH (25 mL) to give 1-(5-bromo-2-pyridinyl)-4-(phenylsulfonyl)piperazine (0.957 g) as a light yellow solid.

Workup

  1. customThe tube was sealed
  2. temperatureAfter that time, the reaction was cooled to room temperature
  3. extractionextracted with EtOAc (2×50 mL)
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customto give a yellow solid

Sources & evidence

ORD record
ord-c464dd54bb8e4e08b9a3040ccfe3d29a
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

Loading…