tert-Butyl piperazine-1-carboxylate → tert-Butyl 4-(4-ethoxy-6-methyl-2-pyridyl)piperazine-1-carboxylate

HRID 1775375Notes

Reaction equation

HRID 1775375 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH3:10])[CH:5]=[C:4]([CH3:11])[N:3]=1.[N:12]1([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1.C(OCC)(=O)C.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]>[CH2:9]([O:8][C:6]1[CH:5]=[C:4]([CH3:11])[N:3]=[C:2]([N:15]2[CH2:14][CH2:13][N:12]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17][CH2:16]2)[CH:7]=1)[CH3:10]

Participants

8

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 89825734HCID 89825734, compound

Product 1

HCID 131734740tert-Butyl 4-(4-ethoxy-6-methyl-2-pyridyl)piperazine-1-carboxylateYield 88%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

2-Bromo-4-ethoxy-6-methylpyridine (108 mg, 0.5 mmol), tert-butyl piperazine-1-carboxylate (140 mg, 0.75 mmol), Pd2(DBA)3 (10 mg, 0.011 mmol), sodium tert-butoxide (80 mg, 0.825 mmol) and BINAP (20 mg, 0.032 mmol) were placed in anhydrous THF (3 ml) under argon and heated at 80° C. for 30 minutes under microwave heating. The mixture was diluted with ethyl acetate, filtered through kieselguhr and concentrated under reduced pressure. The residue was dissolve in DCM and filtered through a plug of silica. The filter was washed with a mixture of DCM and diethylether, the combined filtrates were concentrated to dryness under reduced pressure to give 141 mg (0.44 mmol, 88% yield) MS (multi-mode) m/z=322.2 [M+H]+.

Workup

  1. temperatureheating
  2. filtrationfiltered through kieselguhr
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolve in DCM
  5. filtrationfiltered through a plug of silica
  6. washThe filter was washed with a mixture of DCM and diethylether
  7. concentrationthe combined filtrates were concentrated to dryness under reduced pressure
  8. customto give 141 mg (0.44 mmol, 88% yield)

Sources & evidence

ORD record
ord-f76d732f326b4e1ab73c36a38abebd99
Source dataset
uspto-grants-2016_02
Patent number
US09260441B2

Reaction notes

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