Benzofuran-2-carboxylic acid → Piperazine, 1-(2-benzofuranylcarbonyl)-4-((3,4,5-trimethoxyphenyl)methyl)-, monohydrochloride

HRID 2108097Notes

Reaction equation

HRID 2108097 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([OH:12])=O.[ClH:13].Cl.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31])[CH2:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(P(=O)(OCC)OCC)#N.C(OCC)(=O)C.Cl>CCCCCC.C(OCC)(=O)C.O.CN(C)C=O.C(N(CC)CC)C>[ClH:13].[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([N:24]1[CH2:23][CH2:22][N:21]([CH2:20][C:19]2[CH:27]=[C:28]([O:32][CH3:33])[C:29]([O:30][CH3:31])=[C:17]([O:16][CH3:15])[CH:18]=2)[CH2:26][CH2:25]1)=[O:12]

Participants

10

Reactant 4

HCID 10331Benzofuran-2-carboxylic acidHCID 76257Diethyl cyanophosphonateHCID 128285011-[(3,4,5-Trimethoxyphenyl)methyl]piperazine;dihydrochlorideHCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 3038617Piperazine, 1-(2-benzofuranylcarbonyl)-4-((3,4,5-trimethoxyphenyl)methyl)-, monohydrochlorideYield 47.2%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 2-benzofuranecarboxylic acid (0.5 g), 1-(3,4,5-trimethoxybenzyl)piperazine dihydrochloride (1.1 g), triethylamine (1.2 g) and N,N-dimethylformamide (20 ml) is added dropwise, while stirring at room temperature, diethyl cyanophosphonate (1.2 ml), followed by stirring for one hour at room temperature. After addition of water (100 ml), ethyl acetate (100 ml) and hexane (100 ml), the mixture is extracted with ethyl acetate. The organic layer is washed with water, dried, and concentrated under reduced pressure. The residue is purified by means of a silica gel column chromatography (hexane:ethyl acetate:acetone=1:1:0.5) to give an oily product, to which is added 1N hydrogen chloride - ethyl acetate solution (10 ml) to cause precipitation of powder. The powdery product is collected by filtration and recrystallized from a mixture of methanol - ethyl acetate to give 1-(2-benzofuranylcarbonyl)4-(3,4,5-trimethoxybenzyl)piperazine hydrochloride (0.65 g) as colorless needles, m.p. 221°-225° C. (decomp.).

Workup

  1. additionis added dropwise
  2. stirringby stirring for one hour at room temperature
  3. extractionthe mixture is extracted with ethyl acetate
  4. washThe organic layer is washed with water
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by means of a silica gel column chromatography (hexane:ethyl acetate:acetone=1:1:0.5)
  8. customto give an oily product
  9. customprecipitation of powder
  10. filtrationThe powdery product is collected by filtration
  11. customrecrystallized from a mixture of methanol - ethyl acetate

Sources & evidence

ORD record
ord-c9010a967ad149b091f9d325d01e6853
Source dataset
uspto-grants-1990_06
Patent number
US04937246

Reaction notes

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