Sodium Hydroxide → N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]isonicotinthioamide

Temperature

100 °C

Lawesson's reagent (328 mg, 0.811 mmol, commercially available product) was added to a toluene (2.5 ml) solution of N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]isonicotinamide (SRPIN-1, GIF-0340) (528 mg, 1.51 mmol), obtained as described in Referential Example 1-3, and the resulting mixture was stirred with refluxing at 100° C. for 12 hours. The mixture was cooled to room temperature, and then an aqueous solution of 2 M sodium hydroxide was added thereto to alkalify the solution. The mixture was reverse extracted three times with an aqueous solution of 12 M sodium hydroxide. 2 M hydrochloric acid was added to the aqueous layer to acidify the solution. Then, the resulting mixture was extracted three times with ether. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (50 g, hexane/ethyl acetate=1/1). Thus, N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]isonicotinthioamide (GIF-0616) (186 mg, 33.7%) was yielded as a colorless solid.

1. customobtained
2. temperatureThe mixture was cooled to room temperature
3. extractionThe mixture was reverse extracted three times with an aqueous solution of 12 M sodium hydroxide
4. addition2 M hydrochloric acid was added to the aqueous layer
5. extractionThen, the resulting mixture was extracted three times with ether
6. washThe obtained organic layer was washed with a saturated sodium chloride solution
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel column chromatography (50 g, hexane/ethyl acetate=1/1)

ORD record

ord-0f4b57d8b875461b9cc6986809cc74f8

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08338362B2