Diisopropylethylamine → tert-Butyl 4-(5-bromo-3-methylpyridin-2-yl)piperazine-1-carboxylate

HRID 2195052Notes

Reaction equation

HRID 2195052 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([Br:9])=[CH:4][N:3]=1.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].CCN(C(C)C)C(C)C>CC(N(C)C)=O>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][N:20]([C:2]2[C:7]([CH3:8])=[CH:6][C:5]([Br:9])=[CH:4][N:3]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 8176802,5-Dibromo-3-methylpyridine

Product 1

HCID 46739269tert-Butyl 4-(5-bromo-3-methylpyridin-2-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Heat a solution of 2,5-dibromo-3-methyl-pyridine (Chontech Inc.) (12.6 g, 50.3 mmol), piperazine-1-carboxylic acid tert-butyl ester (11.7 g, 62.9 mmol) and DIEA (13.3 g, 102.0 mmol) in DMA at 130° C. for 36 h. Partition the dark brown reaction mixture between water and EtOAc. Wash the EtOAc layer with water (1×) and brine (1×), dry (Na2SO4) and concentrate under reduced pressure to give the crude product. Purify by flash chromatography, eluting with 9:1 hexanes:EtOAc, increasing to 3:1 hexanes:EtOAc to provide the title compound as a solid.

Workup

  1. customPartition the dark brown reaction mixture between water and EtOAc
  2. washWash the EtOAc layer with water (1×) and brine (1×)
  3. dry with materialdry (Na2SO4)
  4. concentrationconcentrate under reduced pressure
  5. customto give the crude product
  6. customPurify by flash chromatography
  7. washeluting with 9:1 hexanes
  8. temperatureEtOAc, increasing to 3:1 hexanes

Sources & evidence

ORD record
ord-0172bdeeda314b9d9a7865bc2ace6fa7
Source dataset
uspto-grants-2012_12
Patent number
US08334382B2

Reaction notes

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