Piperazine → 1-(2,3-Dihydro-benzofuran-2-ylmethyl)-piperazine

HRID 1772218Notes

Reaction equation

HRID 1772218 reaction equation
I[CH2:2][CH:3]1[CH2:7][C:6]2[CH:8]=[CH:9][CH:10]=[CH:11][C:5]=2[O:4]1.C(=O)([O-])[O-].[K+].[K+].[NH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1>C(#N)C>[O:4]1[C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[CH2:7][CH:3]1[CH2:2][N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 4837PiperazineHCID 11430Potassium CarbonateHCID 3255132-(Iodomethyl)-2,3-dihydro-1-benzofuran

Product 1

HCID 31596641-(2,3-Dihydro-benzofuran-2-ylmethyl)-piperazineYield 54%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-(iodomethyl)-2,3-dihydro-1-benzofuran (5.3 g, 20.4 mmol) in acetonitrile (70 ml) was added potassium carbonate (5.6 g, 40.5 mmol, 2 eq) and piperazine (8.8 g, 102.2 mmol, 5 eq). The resulting mixture was heated at reflux for 2 hours. The solids were then filtered off and the filtrate was concentrated under vacuum. The crude material was purified by silica gel chromatography using 0.5-2.5% methanol in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 1-(2,3-dihydro-1-benzofuran-2-ylmethyl)piperazine as brown oil (2.4 g, 54%); (ES, m/z): [M+H]+ 219; 1H NMR (300 MHz, CDCl3): δ 7.07-7.17 (m, 2H), 6.78-6.85 (m, 2H), 4.92-5.01 (m, 1H), 3.22 (dd, J=9.0 Hz, 15.6 Hz, 1H), 2.91-2.99 (m, 4H), 2.71-2.82 (m, 1H), 2.53-2.71 (m, 6H).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 2 hours
  3. filtrationThe solids were then filtered off
  4. concentrationthe filtrate was concentrated under vacuum
  5. customThe crude material was purified by silica gel chromatography
  6. washto elute
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-f5d1171d16f7463c968d1fad145c89e9
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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