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

HRID 912160Notes

Reaction equation

HRID 912160 reaction equation
C1(C)C=CC=CC=1.Br[C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].CC(C)([O-])C.[K+]>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].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.O>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

8

Reactant 4

HCID 1140TolueneHCID 122863-BromopyridineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 11673373Tert-butyl 4-(pyridin-3-YL)piperazine-1-carboxylateYield 102.5%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A toluene solution (6 ml) of 3-bromopyridine (300 mg, 1.89 mmol), piperazine-1-carboxylic acid tert-butyl ester (389 mg, 2.09 mmol), tris(dibenzylideneacetone)dipalladium (43.4 mg, 0.0474 mmol), Xantphos (54.9 mg, 0.0949 mmol) and potassium tert butoxide (469 mg, 4.18 mmol) was degassed under ultrasonic irradiation, and stirred at 80° C. for 17 hours under a nitrogen atmosphere. After the reaction mixture was cooled to room temperature, water (20 ml) was added, followed by extraction twice with dichloromethane (20 ml). The organic layer was dried over sodium sulfate, followed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane/methanol=30/1), to obtain a crude product of 4-pyridin-3-yl-piperazine-1-carboxylic acid tert-butyl ester as a yellow liquid (510 mg).

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction twice with dichloromethane (20 ml)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationfollowed by concentration under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (dichloromethane/methanol=30/1)

Sources & evidence

ORD record
ord-e9b2efc3102c4ed2b2b8cd69776da559
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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