Sodium Iodide → tert-Butyl piperazine-1-carboxylate

HRID 565201Notes

Reaction equation

HRID 565201 reaction equation
N1C=CC(CNC(C2C3OCCOC=3C=CC=2)=O)=CC=1.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][N:31](S(CCCI)(=O)=O)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].[I-].[Na+]>C(#N)C.CO.O.[Pt](=O)=O>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

8

Reactant 3

HCID 5238Sodium IodideHCID 212680472,3-Dihydro-N-(4-pyridinylmethyl)-1,4-benzodioxin-5-carboxamideHCID 54399062HCID 54399062, compound

Product 1

HCID 143452tert-Butyl piperazine-1-carboxylateYield 39%

Reagents, catalysts & solvents 4

HCID 345198Adams' catalystCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A stirred solution of the 2,3-dihydrobenzo[1,4]dioxine-5-carboxylic acid (pyridin-4-ylmethyl)amide (1.30 g, 4.8 mmol) and 4-(3-iodopropane-1-sulfonyl)piperazine-1-carboxylic acid tert-butyl ester (prepared from the corresponding chloro compound by treatment with sodium iodide in actone) (2.12 g, 5.1 mmol) in acetonitrile (25 mL) was heated under reflux for 8 hours. The mixture was concentrated in vacuo and the residue was triturated with ethyl acetate. Filtration gave the crude pyridinium iodide which was dissolved in methanol (25 mL) and water (5 mL), and hydrogenated over platinum(IV) oxide (450 mg) at atmospheric pressure for 16 hours. The mixture was filtered through Celite® and the filtrate was partitioned between dichloromethane and aqueous ammonium hydroxide. The dichloromethane was dried (Na2SO4) and evaporated in vacuo. Purification of the residue by silica gel chromatography gave 4-[3-(4-{[2,3-dihydrobenzo[1,4]dioxin-5-carbonyl)amino]methyl}pyridin-1-yl)propane-1-sulfonyl]piperazine-1-carboxylic acid tert-butyl ester (1.05 g, 39%).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 8 hours
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue was triturated with ethyl acetate
  5. filtrationFiltration
  6. customgave the crude pyridinium iodide which
  7. filtrationThe mixture was filtered through Celite®
  8. customthe filtrate was partitioned between dichloromethane and aqueous ammonium hydroxide
  9. dry with materialThe dichloromethane was dried (Na2SO4)
  10. customevaporated in vacuo
  11. customPurification of the residue by silica gel chromatography

Sources & evidence

ORD record
ord-8c707df9cdcb409bbb66fdfc6779fe03
Source dataset
uspto-grants-2001_01
Patent number
US06172062B2

Reaction notes

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