Sodium Carbonate → 1-(2,5-Difluorophenyl)piperazine

A mixture of 2,5-difluoroaniline (2.58 g, 20 mmol) and bis(2-chloroethyl)amine hydrochloride (3.96 g, 22 mmol) in butanol (10 mL) was heated at reflux for 24 hours. The mixture was cooled to room temperature, sodium carbonate (2.33 g, 22 mmol) was added, and the mixture was heated again at reflux. After 2 days, the mixture was cooled to room temperature, hexane (15 mL) and 3 N NaOH (25 mL) were added, and the resulting layers were separated. The aqueous layer was extracted with chloroform (3×25 mL) and the combined organic fractions were flashed over a column of silica gel. The silica gel was further eluted with a gradient of chloroform to chloroform/methanol (4:1). The solvent was removed from the combined fractions with Rf=0.14 [silica gel, chloroform/methanol (4:1)], giving the title compound as a yellow oil (0.606 g, 3.1 mmol, 15%). ESI-MS m/z 199 (MH+).

1. temperaturewas heated
2. temperatureat reflux for 24 hours
3. temperaturethe mixture was heated again
4. temperatureat reflux
5. temperaturethe mixture was cooled to room temperature
6. customthe resulting layers were separated
7. extractionThe aqueous layer was extracted with chloroform (3×25 mL)
8. washThe silica gel was further eluted with a gradient of chloroform to chloroform/methanol (4:1)
9. customThe solvent was removed from the combined fractions with Rf=0.14 [silica gel, chloroform/methanol (4:1)]

ORDレコード

ord-8bbc93ece06e41dd9a85ff2fe791855c

出典データセット

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06706716B2