Ammonium Chloride → HCID 121317107, compound

Temperature

60 °C

To a suspension of (S)-6-(difluoromethyl)-5,5-difluoro-6-(2-fluoro-5-nitrophenyl)piperidine-2-thione (1.00 g, 2.94 mmol) in ethanol (15 mL) and water (4 mL) was added iron powder (821 mg, 145 mmol) and NH4Cl (786 mg, 14.7 mmol, 5.0 Eq). The black mixture was stirred at 60° C. for 18 hours. After the reaction mixture was cooled to 25° C., the crude product was filtered and the residue was washed with ethanol (100 mL). The combined filtrates were concentrated and the resulting solid was dispersed in ethyl acetate (100 mL). The mixture was filtered and the filtrate was washed with water (30 mL), brine (20 mL) and concentrated. The crude product was purified by flash chromatography on silica (petroleum ether:ethyl acetate=3:1˜2:1) to give (S)-6-(5-amino-2-fluorophenyl)-6-(difluoromethyl)-5,5-difluoropiperidine-2-thione (819 mg, 2.51 mmol, 85.3% yield). 1H NMR (DMSO-d6, 400 MHz): δ 10.97 (s, 1H), 7.03-6.90 (m, 2H), 6.64-6.55 (m, 2H), 5.19 (s, 2H), 3.19-3.15 (m, 1H), 3.03-2.94 (m, 1H), 2.35-2.24 (m, 2H).

1. temperatureAfter the reaction mixture was cooled to 25° C.
2. filtrationthe crude product was filtered
3. washthe residue was washed with ethanol (100 mL)
4. concentrationThe combined filtrates were concentrated
5. additionthe resulting solid was dispersed in ethyl acetate (100 mL)
6. filtrationThe mixture was filtered
7. washthe filtrate was washed with water (30 mL), brine (20 mL)
8. concentrationconcentrated
9. customThe crude product was purified by flash chromatography on silica (petroleum ether:ethyl acetate=3:1˜2:1)

ORD record

ord-231a6ab8a1ec4e9bae865a8b5aeb6ac3

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346797B1