Piperazine → 1-[(5-Chloro-2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine

HRID 1772226Notes

Reaction equation

HRID 1772226 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]([CH2:10]Cl)[CH2:7][C:6]=2[CH:12]=1.[NH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]([CH2:10][N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[CH2:7][C:6]=2[CH:12]=1

Participants

3

Reactant 2

HCID 4837PiperazineHCID 867194765-Chloro-2-(chloromethyl)-2,3-dihydro-1-benzofuran

Product 1

HCID 663615131-[(5-Chloro-2,3-dihydro-1-benzofuran-2-yl)methyl]piperazineYield 65.1%

Conditions

Temperature
135 °C

Procedure

To 5-chloro-2-(chloromethyl)-2,3-dihydro-1-benzofuran (1.6 g, 7.9 mmol) was added piperazine (2.72 g, 31.6 mmol, 4 eq) with stirring for 15 hours at 135° C. in an oil bath. The crude material was purified by silica gel chromatography using 3% dichloromethane in methanol to elute. The product-containing fractions were combined and concentrated under vacuum to afford 1-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine as a light yellow solid (1.3 g, 65%); (ES, m/z): [M+H]+ 253; 1H NMR (300 MHz, CDCl3): δ 7.03-7.11 (m, 2H), 6.68 (d, J=8.4 Hz, 1H), 4.93-5.03 (m, 1H), 3.20-3.29 (m, 1H), 2.88-2.99 (m, 6H), 2.72-2.79 (m, 1H), 2.49-2.63 (m, 5H).

Workup

  1. customThe crude material was purified by silica gel chromatography
  2. washto elute
  3. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-bda7648e12e74a469286ff41b6253cf4
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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