Ethylene Glycol → Tert-butyl 4-(5-bromopyridin-3-yl)piperazine-1-carboxylate

HRID 1044562Notes

Reaction equation

HRID 1044562 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6](I)[CH:7]=1.[N:9]1([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(O)CO>C(O)(C)C.[Cu]I>[C:18]([O:17][C:15]([N:9]1[CH2:14][CH2:13][N:12]([C:6]2[CH:5]=[N:4][CH:3]=[C:2]([Br:1])[CH:7]=2)[CH2:11][CH2:10]1)=[O:16])([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 62657Potassium Phosphate, TribasicHCID 143452tert-Butyl piperazine-1-carboxylateHCID 8204093-Bromo-5-iodopyridine

Product 1

HCID 11653049Tert-butyl 4-(5-bromopyridin-3-yl)piperazine-1-carboxylateYield 37%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3776IsopropanolSolvent

Procedure

A solution of 3-bromo-5-iodopyridine (13.0 g, 45.8 mmol), tert-butyl piperazine-1-carboxylate (8.53 g, 45.8 mmol), copper(I) iodide (0.871 g, 4.57 mmol), K3PO4 (19.46 g, 91.68 mmol), 1,2-ethanediol (5.1 mL, 91 mmol) in isopropyl alcohol (80 mL) in a sealed tube was heated at 80° C. in an oil bath for 2 days. After cooling to room temperature, the reaction mixture was filtered through celite. The filtrate was concentrated in vacuo. The residue was taken up in EtOAc and the solution was washed with saturated NaHCO3, dried (MgSO4) and concentrated. Purification by flash chromatography on silica gel (20% EtOAc/hexanes to 30% EtOAc/hexanes) afforded 5.75 g (37%) of desired product. MS calculated for C14H20BrN3O2: (M+H) 343; found 342.0, 344.0.

Workup

  1. filtrationthe reaction mixture was filtered through celite
  2. concentrationThe filtrate was concentrated in vacuo
  3. washthe solution was washed with saturated NaHCO3
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customPurification by flash chromatography on silica gel (20% EtOAc/hexanes to 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-583448f49ff04c2c8f05d7547c739272
Source dataset
uspto-grants-2013_10
Patent number
US08563582B2

Reaction notes

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