2-Bromopyridine → (S)-1,4-dibenzyl-2-(2-pyridinyl-ethyl)-piperazine

HRID 1350361Notes

Reaction equation

HRID 1350361 reaction equation
C12BC(CCC1)CCC2.[CH2:10]([N:17]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:19][C@@H:18]1[CH:30]=[CH2:31])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][N:53]=1.[OH-].[Na+]>Cl.[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>[CH2:10]([N:17]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:19][C@@H:18]1[CH2:30][CH2:31][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][N:53]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

8

Reactant 5

HCID 79732-BromopyridineHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 17759473(S)-1,4-dibenzyl-2-vinylpiperazine

Product 1

HCID 17759583(S)-1,4-dibenzyl-2-(2-pyridinyl-ethyl)-piperazineYield 79%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 313Hydrochloric AcidSolvent2×

Procedure

Combine 9-borabicyclo[3.3.1]nonane (62.6 mL, 31.3 mmol, 0.5 M in THF) and (S)-1,4-dibenzyl-2-vinyl-piperazine. (2.29 g, 7.83 mmol) and stir at ambient temperature. After 18 hours, add triphenylphosphine (657 mg, 2.50 mmol), tetrakis(triphenylphosphine) palladium(0) (362 mg, 0.31 mmol), and 2-bromopyridine (1.12 mL, 11.7 mmol). Add 3M NaOH (6.4 mL, 19.3 mmol) slowly, and gas evolution will occur. Heat at reflux. After 24 hours, cool to ambient temperature, add 5N HCl (50 mL), and stir 1 hour. Dilute with 0.2 N HCl, extract with diethyl ether, and discard the diethyl ether extracts. Add 5N NaOH to the acidic aqueous solution until pH is 12–14. Extract with diethyl ether. Wash the diethyl ether extracts with water and brine, dry over sodium sulfate, filter and concentrate under reduced pressure. Purify by silica gel chromatography using 2N ammonia in methanol-methylene chloride (0.5%–3%) as the eluent to give the title compound (2.3 g, 79%): mp 83–86° C.; mass spectrum (ion spray): m/z=372 (M+1). Analysis calculated for C25H29N3: C, 80.82; H, 7.87; N, 11.31. Found: C, 80.56; H, 7.60; N, 11.30.

Workup

  1. temperatureHeat
  2. temperatureat reflux
  3. waitAfter 24 hours
  4. temperaturecool to ambient temperature
  5. stirringstir 1 hour
  6. extractionextract with diethyl ether
  7. additionAdd 5N NaOH to the acidic aqueous solution until pH is 12–14
  8. extractionExtract with diethyl ether
  9. washWash the diethyl ether
  10. dry with materialdry over sodium sulfate
  11. filtrationfilter
  12. concentrationconcentrate under reduced pressure
  13. customPurify by silica gel chromatography

Sources & evidence

ORD record
ord-b9d23186f8054370a736756ea6ac7fd7
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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