Ammonium Chloride → HCID 9835197, compound

Temperature

70 °C

A mixture of 3-chloro-4-fluoronitrobenzene (0.070 g, 0.4 mmol) and thiomorpholine (0.165 g, 1.6 mmol) was stirred at 70° C. for 16 hours. The reaction mixture was cooled down to room temperature, concentrated under a reduced pressure and purified by a silica gel column chromatography (developing solvents; chloroform:methanol=9:1) to obtain yellow powdery crystals. Iron powder (0.27 g, 4.83 mmol), isopropanol (0.5 ml) and 1 equivalent of aqueous solution of ammonium chloride (0.12 ml, 0.12 mol) were added thereto, followed by stirring at 70° C. for 16 hours. The reaction mixture was cooled down to room temperature, tetrahydrofuran (0.4 ml) was added thereto and insoluble matters were filtered off using Celite, followed by washing with ethyl acetate (0.4 ml) for four times. The filtrate was concentrated under a reduced pressure and methanol (0.4 ml) and dimethylformamide dimethylacetal (0.095 g, 0.8 mmol) were added thereto, followed by stirring at 70° C. for 64 hours. The reaction mixture was cooled down to room temperature and concentrated under a reduced pressure and methanol (0.4 ml) and hydroxylamine hydrochloride (0.033 g, 0.48 mmol) were added thereto, followed by stirring at room temperature for 6 hours. The reaction mixture was concentrated under a reduced pressure and a saturated aqueous solution of sodium hydrogen carbonate (0.4 ml) was added thereto, followed by extracting with ethyl acetate. The organic layer was concentrated under a reduced pressure, purified by an NH type silica gel column chromatography (developing solvents; n-hexane:ethyl acetate=1:1) and recrystallized from ethyl acetate/n-hexane to obtain the title compound (0.026 g) (the compound 3 in Table 1 which will be shown after) in colorless powder.

1. temperatureThe reaction mixture was cooled down to room temperature
2. concentrationconcentrated under a reduced pressure
3. custompurified by a silica gel column chromatography (developing solvents; chloroform:methanol=9:1)
4. customto obtain yellow powdery crystals
5. stirringby stirring at 70° C. for 16 hours
6. temperatureThe reaction mixture was cooled down to room temperature
7. filtrationinsoluble matters were filtered off
8. washby washing with ethyl acetate (0.4 ml) for four times
9. additionwere added
10. stirringby stirring at 70° C. for 64 hours
11. temperatureThe reaction mixture was cooled down to room temperature
12. additionwere added
13. stirringby stirring at room temperature for 6 hours
14. concentrationThe reaction mixture was concentrated under a reduced pressure
15. additiona saturated aqueous solution of sodium hydrogen carbonate (0.4 ml) was added
16. extractionby extracting with ethyl acetate
17. concentrationThe organic layer was concentrated under a reduced pressure
18. custompurified by an NH type silica gel column chromatography (developing solvents; n-hexane:ethyl acetate=1:1)
19. customrecrystallized from ethyl acetate/n-hexane

ORD record

ord-f0706e0513b74607a5ff50faccec833f

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07214714B2