Nitric Acid → HCID 118307918, compound

Temperature

0 °C

(6R)-3,5,5-Trifluoro-6-(2-fluorophenyl)-3,6-dimethylpiperidin-2-one (1.86 g, 6.76 mmol) (1:1.8 mixture of diastereomers) was suspended in trifluoroacteic acid (11.5 ml, 149 mmol). The mixture was cooled to 0° C. and concentrated H2SO4 (2.86 ml, 52.0 mmol, 97%) was added. Finally, fuming HNO3 (0.33 ml, 7.4 mmol) was added in a dropwise manner and the reaction was stirred at 0° C. for 10 min. The reaction mixture was poured onto 150 g ice and basified to pH>11 using 5 M NaOH. The resulting suspension was extracted with ethyl acetate (250 mL). The phases were separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organics were washed with a solution of saturated aqueous NH4Cl (50 mL) and water (50 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to afford (6R)-3,5,5-trifluoro-6-(2-fluoro-5-nitrophenyl)-3,6-dimethylpiperidin-2-one (2.08 g, 6.50 mmol, 96% yield) (1:1.8 mixture of diastereomers) LC-MS (m/z) 321.1 (MH+) tR=0.62 minutes (Method B).

1. extractionThe resulting suspension was extracted with ethyl acetate (250 mL)
2. customThe phases were separated
3. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
4. washThe combined organics were washed with a solution of saturated aqueous NH4Cl (50 mL) and water (50 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure

ORD record

ord-190b70c859924c6caac50f714b5473a8

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09353084B2