Acetic Acid → trans-6-(2,5-Difluorophenyl)-5-nitro-1-(2-pyridin-2-ylethyl)piperidin-2-one

To a solution of 2,5-difluorobenzaldehyde (2.29 mL, 21.1 mmol) in ethanol (42 mL) was added methyl 4-nitrobutyrate (2.51 mL, 21.1 mmol) and the mixture stirred for 5 min. To the reaction mixture was added 2-pyridin-2-ylethanamine (2.61 mL, 21.1 mmol) and the mixture stirred for 10 min. To the mixture was added sodium acetate (1.73 g, 21.1 mmol) followed by glacial acetic acid (2.42 mL, 42.2 mmol) and the mixture heated at reflux temperature for 48 h. The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (25 mL) and the aqueous phase extracted with ethyl acetate (4×25 mL). The combined organic phases were washed with saturated aqueous brine (1×25 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed in vacuo. The yellow oil was purified by column chromatography (silica gel Biotage 40S™) eluting with ethyl acetate/hexane (gradient from 0% to 100%) to give the racemic trans title compound as a yellow gum. LC/MS 362.2 (M+1).

1. stirringthe mixture stirred for 10 min
2. temperaturethe mixture heated
3. temperatureat reflux temperature for 48 h
4. customThe solvent was removed in vacuo and to the yellow oil
5. additionwas added saturated aqueous sodium hydrogen carbonate (25 mL)
6. extractionthe aqueous phase extracted with ethyl acetate (4×25 mL)
7. washThe combined organic phases were washed with saturated aqueous brine (1×25 mL)
8. dry with materialdried with anhydrous sodium sulfate
9. filtrationfiltered
10. customthe solvent removed in vacuo
11. customThe yellow oil was purified by column chromatography (silica gel Biotage 40S™)
12. washeluting with ethyl acetate/hexane (gradient from 0% to 100%)

ORD record

ord-4d534f968d3b48e4bf576eecbea863bb

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653059B2