1-Methylpiperazine → 1-[2-Hydroxy-5-(4-methylpiperazin-1-yl)phenyl]ethanone

HRID 45805

Reaction equation

HRID 45805 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[CH3:12][N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1>C1COCC1.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]>[OH:11][C:5]1[CH:4]=[CH:3][C:2]([N:16]2[CH2:17][CH2:18][N:13]([CH3:12])[CH2:14][CH2:15]2)=[CH:7][C:6]=1[C:8](=[O:10])[CH3:9]

Participants

5

Reactant 2

HCID 531671-MethylpiperazineHCID 959915'-Bromo-2'-hydroxyacetophenone

Product 1

HCID 679739361-[2-Hydroxy-5-(4-methylpiperazin-1-yl)phenyl]ethanoneYield 51%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

1-(5-bromo-2-hydroxyphenyl)ethanone 1.0 g (4.65 mmol) in THF (10 ml), N-methylpiperazine 0.83 ml (7.45 mmol), LiHMDSA 16.2 ml (16.2 mmol), Pd2(dba)3 68 mg (0.074 mmol) and 2-dicyclohexylphosphino-2′-N,N-dimethylaminobiphenyl 29.3 mg (0.074 mmol) were combined under argon in a capped vial and stirred at 70° C. for 40 minutes. The volatiles were removed in vacuo, the obtained residue was dissolved with water and 1 N HCl (pH=6) and portioned with DCM. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (DCM gradient to 10% MeOH/DCM) to provide 532 mg (51%) of desired product as a brown solid. LC/MS (254 nm) HPLC method 2 Rt 3.34 min. 1H NMR (401 MHz, DMSO-d6) δ 11.45 (s, 1H), 7.21-7.28 (m, 2H), 6.80-6.93 (m, 1H), 2.98-3.10 (m, 4H), 2.63 (s, 3H), 2.44-2.48 (m, 4H), 2.23 (s, 3H). HRMS (ESI) calcd for C13H18N2O2 [M+H]+ 235.1441 Found 235.1448.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe obtained residue was dissolved with water and 1 N HCl (pH=6)
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography (DCM gradient to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-aeb794bda26b4d999630502e62d6f8b9
Source dataset
uspto-grants-2013_09
Patent number
US08541576B2

Linked notes

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