Piperazine → 1-(2-fluoro-4-nitrophenyl)piperazine

A solution of 12.0 g (75.42 mmol) of 3,4-difluoronitrobenzene (2) in 150 mL of acetonitrile was treated with 16.24 g (188.6 mmol) of piperazine, followed by warming at reflux for 3 hours. The solution was cooled to ambient temperature and was concentrated in vacuo. The residue was diluted with 200 mL of water and was extracted with ethyl acetate (3×250 mL). The combined organic layers were extracted with water (200 mL) and saturated NaCl solution (200 mL), followed by drying (Na2SO4). The solution was concentrated in vacuo to afford an orange oil which was chromatographed over 450 g of 230-400 mesh silica gel eluting initially with dichloromethane until the least polar fractions had eluted and then elution was continued with 2% (v/v) methanol-chloroform and then with 10% (v/v) methanol-chloroform. These procedures afforded 13.83 g (81%) of the desired piperazine derivative 3, mp=68.5°-71° C.

1. temperatureby warming
2. temperatureat reflux for 3 hours
3. concentrationwas concentrated in vacuo
4. additionThe residue was diluted with 200 mL of water
5. extractionwas extracted with ethyl acetate (3×250 mL)
6. extractionThe combined organic layers were extracted with water (200 mL) and saturated NaCl solution (200 mL)
7. dry with materialby drying (Na2SO4)
8. concentrationThe solution was concentrated in vacuo
9. customto afford an orange oil which
10. customwas chromatographed over 450 g of 230-400 mesh silica gel eluting initially with dichloromethane until the least polar fractions
11. washhad eluted
12. washelution

ORD record

ord-ce67a9f661ac49798f3401e77fefa0d5

Source dataset

uspto-grants-1997_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05700799