Hydrochloric Acid → 1-[2-(Methylsulfanyl)-5-(trifluoromethoxy)phenyl]methanamine hydrochloride

(Step 1) A mixture of 2-fluoro-5-(trifluoromethoxy)benzonitrile (6.55 g) and sodium methanethiolate (2.46 g) was stirred in N,N-dimethylformamide (50 ml) at room temperature for 3 hr. The reaction solution was treated with 1N hydrochloric acid, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. A solution of the obtained residue in tetrahydrofuran (20 ml) was added at 0° C. to a suspension of lithium aluminum hydride (1.45 g) in tetrahydrofuran (250 ml). The mixture was stirred at room temperature for 2 hr, and treated with sodium sulfate 10 hydrate. The mixture was further stirred at room temperature for 30 min, and the inorganic substance was filtered off through celite. The filtrate was concentrated under reduced pressure. The residue was dissolved in methanol, and 4N hydrogen chloride-ethyl acetate solution (10 ml) was added. The mixture was crystallized from methanol-ethyl acetate to give 1-[2-(methylsulfanyl)-5-(trifluoromethoxy)phenyl]methanamine hydrochloride (4.3 g).

1. extractionextracted with ethyl acetate
2. washThe extract was washed with saturated brine
3. dry with materialdried over magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. additionA solution of the obtained residue in tetrahydrofuran (20 ml) was added at 0° C. to a suspension of lithium aluminum hydride (1.45 g) in tetrahydrofuran (250 ml)
6. additiontreated with sodium sulfate 10 hydrate
7. stirringThe mixture was further stirred at room temperature for 30 min
8. filtrationthe inorganic substance was filtered off through celite
9. concentrationThe filtrate was concentrated under reduced pressure
10. dissolutionThe residue was dissolved in methanol
11. addition4N hydrogen chloride-ethyl acetate solution (10 ml) was added
12. customThe mixture was crystallized from methanol-ethyl acetate

ORD record

ord-0cd921a957fd42beb40241c089c362fb

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481569B2