1-Acetylpiperazine → HCID 57499619, compound

HRID 1907396Notes

Reaction equation

HRID 1907396 reaction equation
[ClH:1].[S:2]1[CH:6]=[CH:5][C:4]2[C:7]([N:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][O:20][C:21]4[C:26]([CH3:27])=[CH:25][C:24](Br)=[CH:23][C:22]=4[O:29][CH3:30])[CH2:13][CH2:12]3)=[CH:8][CH:9]=[CH:10][C:3]1=2.[C:31]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)(=[O:33])[CH3:32].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.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[ClH:1].[C:31]([N:34]1[CH2:39][CH2:38][N:37]([C:24]2[CH:25]=[C:26]([CH3:27])[C:21]([O:20][CH2:19][CH2:18][CH2:17][N:14]3[CH2:15][CH2:16][N:11]([C:7]4[C:4]5[CH:5]=[CH:6][S:2][C:3]=5[CH:10]=[CH:9][CH:8]=4)[CH2:12][CH2:13]3)=[C:22]([O:29][CH3:30])[CH:23]=2)[CH2:36][CH2:35]1)(=[O:33])[CH3:32]

Participants

7

Reactant 4

HCID 837951-AcetylpiperazineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 66647361HCID 66647361, compound

Product 1

HCID 57499619HCID 57499619, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

1-benzo[b]thiophen-4-yl-4-[3-(4-bromo-2-methoxy-6-methylphenoxy)propyl]piperazine hydrochloride (0.5 g, 0.98 mmol), 1-acetyl piperazine (0.15 g, 1.2 mmol), palladium acetate (11 mg, 0.048 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphtyl (BINAP)(63 mg, 0.098 mmol) and sodium t-butoxide (0.23 g, 2.3 mmol) were added to toluene (10 ml) and the mixture was stirred under an argon atmosphere at 90° C. for 22 hours. The reaction mixture was cooled to room temperature and filtrated by cerite. The filter cake was washed with ethyl acetate. The filtrate and wash liquid were combined and thereafter concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (n-hexane:ethyl acetate=11:1→1:1). The purified product was concentrated under reduced pressure and the residue was dissolved in ethyl acetate. A 1N hydrochloric acid/ethanol solution was added to this and the crystal produced was filtrated and dried to obtain 1-acetyl-4-{4-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-3-methoxy-5-methylphenyl}-piperazin hydrochloride (75 mg, 14% yield) as white powder.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltrated by cerite
  3. washThe filter cake was washed with ethyl acetate
  4. washThe filtrate and wash liquid
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (n-hexane:ethyl acetate=11:1→1:1)
  7. concentrationThe purified product was concentrated under reduced pressure
  8. dissolutionthe residue was dissolved in ethyl acetate
  9. additionA 1N hydrochloric acid/ethanol solution was added to this and the crystal
  10. customproduced
  11. filtrationwas filtrated
  12. customdried

Sources & evidence

ORD record
ord-b4845093946b4796a9188a5601e1e1c8
Source dataset
uspto-grants-2013_12
Patent number
US08598162B2

Reaction notes

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