Methyl 4-nitrobutyrate → HCID 57518510, compound

To a solution of 2,5-difluorobenzaldehyde (3.82 mL, 35.2 mmol) in ethanol (70 mL) was added methyl 4-nitrobutyrate (4.51 mL, 35.2 mmol) and the mixture was stirred for 5 minutes. To the reaction mixture was added ammonium acetate (5.42 g, 70.4 mmol) and the mixture stirred for 10 minutes at ambient temperature and then heated at reflux temperature for 16 h. The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (100 mL) and the aqueous phase extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with saturated aqueous brine (1×50 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed in vacuo. The yellow racemic product was purified by preparative HPLC on a Berger SFC using ChiralPak AS-H™ column, eluting with 20% MeOH/CO2 to give (5R,6S)-6-(2,5-difluorophenyl)-5-nitropiperidin-2-one [LC/MS 257.1 (M+1)] as the second eluting isomer and the title compound as the first eluting isomer. LC/MS 257.1 (M+1).

1. stirringthe mixture stirred for 10 minutes at ambient temperature
2. temperatureheated
3. temperatureat reflux temperature for 16 h
4. customThe solvent was removed in vacuo and to the yellow oil
5. additionwas added saturated aqueous sodium hydrogen carbonate (100 mL)
6. extractionthe aqueous phase extracted with ethyl acetate (3×50 mL)
7. washThe combined organic phases were washed with saturated aqueous brine (1×50 mL)
8. dry with materialdried with anhydrous sodium sulfate
9. filtrationfiltered
10. customthe solvent removed in vacuo
11. customThe yellow racemic product was purified by preparative HPLC on a Berger SFC
12. washeluting with 20% MeOH/CO2

ORD record

ord-af0d94972a7a435e9f137c1ffa3c2ade

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716482B2