Toluene → 2-Methyl-1-[4-piperazinophenyl]-2-morpholino propan-1-one

HRID 1188295Notes

Reaction equation

HRID 1188295 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:18])[C:9]([CH3:17])([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH3:10])=[CH:4][CH:3]=1.[NH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C1(C)C=CC=CC=1.C1COCC1>C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(P(C(C)(C)C)C1C(C2C=CC=CC=2)=CC=CC=1)(C)C.CC(C)([O-])C.[K+]>[CH3:10][C:9]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)([CH3:17])[C:8]([C:5]1[CH:6]=[CH:7][C:2]([N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[CH:3][CH:4]=1)=[O:18]

Participants

9

Reactant 4

HCID 1140TolueneHCID 4837PiperazineHCID 8028TetrahydrofuranHCID 157024081-(4-Chlorophenyl)-2-methyl-2-(morpholin-4-yl)propan-1-one

Product 1

HCID 579346002-Methyl-1-[4-piperazinophenyl]-2-morpholino propan-1-oneYield 96.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 27342152-(Di-tert-butylphosphino)biphenylCatalystHCID 23665647Potassium tert-butoxideCatalystHCID 3283Diethyl EtherSolvent

Procedure

Further, in a 300 mL four-neck flask provided with a stirrer, a condenser, a thermocouple, and a nitrogen inlet tube, 16 g of 1-(4-chlorophenyl)-2-methyl-2-morpholino-propan-1-one, 20.7 g of piperazine, 140 mg of palladium acetate, 360 mg of (2-biphenyl)di-tert-butylphosphine, 100 mL of toluene, 40 mL of THF, and 9.4 mg of potassium-tert-butoxide were added, followed by reaction at room temperature for 46 hours under a nitrogen stream. The reaction product was diluted with 100 mL of diethyl ether and washed with 100 mL of water, and then an organic layer was dried with anhydrous sodium sulfate. The organic layer was concentrated and then recrystallized with dichloromethane/hexane to produce 18.3 g of 2-methyl-2-morpholin-4-yl-1-(4-piperazinylphenyl)propan-1-one (10). 1H-NMR (CDCl3): 1.34 ppm (s, 6H, —CH3), 2.60 ppm (m, 4H, —CH2—), 3.05 ppm (m, 4H, —CH2—), 3.34 ppm (m, 4H, —CH2—), 3.72 ppm (m, 4H, —CH2), 6.86 ppm (m, 2H, aromatic), 8.58 ppm (m, 2H, aromatic)

Workup

  1. customFurther, in a 300 mL four-neck flask provided with a stirrer, a condenser
  2. customfollowed by reaction at room temperature for 46 hours under a nitrogen stream
  3. washwashed with 100 mL of water
  4. dry with materialan organic layer was dried with anhydrous sodium sulfate
  5. concentrationThe organic layer was concentrated
  6. customrecrystallized with dichloromethane/hexane

Sources & evidence

ORD record
ord-f9aa6a8aee404ccc931e30c8ff98d4db
Source dataset
uspto-grants-2014_03
Patent number
US08674089B2

Reaction notes

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