3-Bromopyridine → Tert-butyl 4-(pyridin-3-YL)piperazine-1-carboxylate

HRID 1640414Notes

Reaction equation

HRID 1640414 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[N:8]1([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([N:11]2[CH2:10][CH2:9][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:13][CH2:12]2)[CH:3]=1

Participants

7

Reactant 3

HCID 122863-BromopyridineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 11673373Tert-butyl 4-(pyridin-3-YL)piperazine-1-carboxylateYield 83.2%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent

Procedure

7.07 g (44.74 mmol) of 3-bromopyridine, 10 g (53.69 mmol) of 1,1-dimethylethyl 1-piperazinecarboxylate, 6.02 g (62.64 mmol) of sodium tert-butoxide and 0.836 g (1.34 mmol) of (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) (BINAP) suspended in 100 ml of toluene are introduced under an inert atmosphere. 0.41 g (0.45 mmol) of [tris(dibenzylideneacetone)dipalladium] (Pd2(dba)3) is then added. The reaction mixture is then refluxed for 22 hours. The mixture is allowed to cool to room temperature, the salts are separated out by filtration through glass fiber and the filtrate is then concentrated under reduced pressure. The residue is taken up in 100 ml of ethyl acetate and 100 ml of water, the aqueous phase is separated out and extracted several times with ethyl acetate, the combined organic phases are washed with saturated aqueous sodium chloride solution and dried over sodium sulfate, and the filtrate is concentrated under reduced pressure. The residue thus obtained is purified by chromatography on silica gel, eluting with a 98/2 and then 95/5 mixture of dichloromethane and methanol. 9.80 g of product are obtained in the form of an oil that crystallizes at room temperature.

Workup

  1. additionare introduced under an inert atmosphere
  2. temperatureThe reaction mixture is then refluxed for 22 hours
  3. customthe salts are separated out by filtration through glass fiber
  4. concentrationthe filtrate is then concentrated under reduced pressure
  5. custom100 ml of water, the aqueous phase is separated out
  6. extractionextracted several times with ethyl acetate
  7. washthe combined organic phases are washed with saturated aqueous sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. concentrationthe filtrate is concentrated under reduced pressure
  10. customThe residue thus obtained
  11. customis purified by chromatography on silica gel
  12. washeluting with a 98/2
  13. addition95/5 mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-4434f613cd1a44e9a8836b8cf239d977
Source dataset
uspto-grants-2012_02
Patent number
US08114866B2

Reaction notes

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