1-(3-Chlorophenyl)ethanone → cis-1-[3-(3,5-Dimethyl-piperazin-1-yl)-phenyl]-ethanone

Temperature

100 °C

An oven-dried MW tube was charged with Pd2(dba)3 (592 mg, 0.65 mmol), K3PO4 (1.92 g, 9.06 mmol) and (2′-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethyl-amine (127 mg, 0.32 mmol). The tube was purged and backfilled with N2 and then 1-(3-chloro-phenyl)-ethanone (1 g, 6.47 mmol), (2R,6S)-2,6-dimethyl-piperazine (886 mg, 7.76 mmol) and DME (10 ml) were added. The mixture was heated in a MW apparatus for 4 h at 100° C. and then further Pd2(dba)3 (592 mg, 0.65 mmol) and (2′-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethyl-amine (127 mg, 0.32 mmol) were added. The reaction mixture was heated to 100° C. for additional 10 h and then the solid was filtered off over a Celite pad. The filtrate was diluted with AcOEt and extracted with 1 M HCl. The aqueous phase was brought to basic conditions with NH4OH and extracted with AcOEt. The organic phase was dried over Na2SO4 and evaporated in vacuo. The crude reaction mixture was purified by column chromatography (eluent: AcOEt/MeOH 8:2) to give 226 mg of 1-[3-((3R,5S)-3,5-dimethyl-piperazin-1-yl)-phenyl]-ethanone.

1. customThe tube was purged
2. temperatureThe reaction mixture was heated to 100° C. for additional 10 h
3. filtrationthe solid was filtered off over a Celite pad
4. additionThe filtrate was diluted with AcOEt
5. extractionextracted with 1 M HCl
6. extractionextracted with AcOEt
7. dry with materialThe organic phase was dried over Na2SO4
8. customevaporated in vacuo
9. customThe crude reaction mixture
10. customwas purified by column chromatography (eluent: AcOEt/MeOH 8:2)

ORD record

ord-0c68304cf3754641a341323b02e2bcfd

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08242175B2