Hydrochloric Acid → HCID 57436051, compound

To a solution of 2-methyl-N-[2-(methylthio)ethyl]-6-nitroaniline (2.6 g, 12 mmol) in ethanol (6.0 mL) was added a solution of Tin(II) chloride dihydrate (7.9 g, 35 mmol) in concd. hydrochloric acid (8.0 mL) at 0° C. and warmed to rt. After 4h, the reaction was quenched by addition of 6N sodium hydroxide (100 mL) and extracted with ethyl acetate (100 mL×2), dried over sodium sulfate, filtered and concentrated. The crude material was dissolved in THF (50 mL) and to this solution was added CDI (2.3 g, 14 mmol) and the mixture was stirred at rt. After 12 h, to the mixture was added CDI (1.5 g, 6.7 mmol) and the reaction mixture was refluxed for 5 h. Then the mixture was cooled to rt and evaporated to dryness. To this was added water (100 mL) and extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with water (50 mL), brine (50 mL), dried over sodium sulfate, filtered and concentrated. The obtained material was dissolved in methanol (30 mL) and to this solution was added 2N sodium hydroxide (3 mL) and stirred at rt for 2 h. Then the mixture was quenched by addition of sat. aq. sodium bicarbonate (50 mL) and extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with water (50 mL), brine (50 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with dichloromethane/methanol (20/1-10/1) to afford 1.8 g (69%) of the title compound.

1. customAfter 4h, the reaction was quenched by addition of 6N sodium hydroxide (100 mL)
2. extractionextracted with ethyl acetate (100 mL×2)
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe crude material was dissolved in THF (50 mL) and to this solution
7. temperaturethe reaction mixture was refluxed for 5 h
8. temperatureThen the mixture was cooled to rt
9. customevaporated to dryness
10. additionTo this was added water (100 mL)
11. extractionextracted with ethyl acetate (100 mL×2)
12. washThe combined organic layers were washed with water (50 mL), brine (50 mL)
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated
16. dissolutionThe obtained material was dissolved in methanol (30 mL) and to this solution
17. additionwas added 2N sodium hydroxide (3 mL)
18. stirringstirred at rt for 2 h
19. customThen the mixture was quenched by addition of sat. aq. sodium bicarbonate (50 mL)
20. extractionextracted with ethyl acetate (100 mL×2)
21. washThe combined organic layers were washed with water (50 mL), brine (50 mL)
22. dry with materialdried over sodium sulfate
23. filtrationfiltered
24. concentrationconcentrated
25. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane/methanol (20/1-10/1)

ORD record

ord-c0615b0489be46adb874b065ce35da28

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08138177B2