1-Methylpiperazine → 5-(4-Methylpiperazin-1-yl)-2-trifluoromethoxyphenylamine

Tris(dibenzilideneacetone)dipalladium, Pd2(dba)3 (1.1 g, 1.2 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)-biphenyl (0.94 g, 2.4 mmol), 5-bromo-2-trifluoromethoxy-phenylamine (30.7 g, 120 mmol) in THF (50 mL) were charged in a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. LiN(TMS)2 solution (1M in THF, 288 mL) and N-methylpiperazine (26.7 mL, 194 mmol) were added and the reaction refluxed for 1 h. The reaction mixture was then allowed to cool to room temperature and filtered through a pad of celite. The organic phase was concentrated, the residue dissolved in DCM (200 ml) and washed with water (1×100 ml). The organic phases were dried over anhydrous Na2SO4, the solvent evaporated in vacuo and the crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10) to afford 21.1 g of 5-(4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamine (64% yield) as a light brown powder.

1. customflushed with argon
2. customThe flask was evacuated
3. temperaturethe reaction refluxed for 1 h
4. filtrationfiltered through a pad of celite
5. concentrationThe organic phase was concentrated
6. dissolutionthe residue dissolved in DCM (200 ml)
7. washwashed with water (1×100 ml)
8. dry with materialThe organic phases were dried over anhydrous Na2SO4
9. customthe solvent evaporated in vacuo
10. customthe crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10)

ORD record

ord-5c613f3e0c7c44888041ef8056620e2e

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08614220B2