tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(6-cyanopyridin-3-yl)piperazine-1-carboxylate

HRID 2100664

Reaction equation

HRID 2100664 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.[N:10]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:8]([C:5]1[N:6]=[CH:7][C:2]([N:13]2[CH2:12][CH2:11][N:10]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14]2)=[CH:3][CH:4]=1)#[N:9]

Participants

7

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 8171545-Bromopyridine-2-carbonitrileHCID 23676156Sodium t-butoxide

Product 1

HCID 67030211Tert-butyl 4-(6-cyanopyridin-3-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

5-Bromo-pyridine-2-carbonitrile (8 mmol), tert-butyl 1-piperazine-carboxylate (9.6 mmol), Pd(dppf)Cl2 (0.24 mmol), dppf (0.36 mmol) and sodium tert-butoxide (11.9 mmol) are mixed in toluene (12 mL) and purged with N2. The mixture is heated in a microwave reactor at 120° C. for 15 minutes, poured into saturated Na2CO3 solution and extracted with EtOAc. The combined extracts are washed with saturated aqueous NaCl and dried over Na2SO4. After concentration, the residue is purified by silica gel chromatography (2:1 hexanes/EtOAc) to give tert-butyl 4-(6-cyano-pyridin-3-yl)-piperazine-1-carboxylate.

Workup

  1. custompurged with N2
  2. additionpoured into saturated Na2CO3 solution
  3. extractionextracted with EtOAc
  4. washThe combined extracts are washed with saturated aqueous NaCl
  5. dry with materialdried over Na2SO4
  6. concentrationAfter concentration
  7. customthe residue is purified by silica gel chromatography (2:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-ba3598acb7104e6bb407b1de0f1fbc2d
Source dataset
uspto-grants-2009_08
Patent number
US07572811B2

Linked notes

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