Hydrochloric Acid → HCID 59306516, compound

Temperature

-10 °C

3-Cyano-2,4,5-trifluorobenzoylethyl acetate (883 mg, 3.25 mmol) was dissolved in ethyl orthoformate (1.35 mL, 8.13 mmol). Acetic anhydride (1.07 mL, 11.4 mmol) was added thereto, and the resultant mixture was stirred at 100° C. for 5 hours. The reaction mixture was concentrated under reduced pressure and co-boiled with toluene (5 mL×3). The residue was dissolved in dichloromethane (20 mL). A 2-(S)-fluoro-1-(R)-cyclopropylamine p-toluenesulfonic acid salt (964 mg, 3.90 mmol) was added thereto, triethylamine (679 μL, 4.88 mmol) was added dropwise to the resultant mixture under stirring at −10° C. After completion of dropwise addition, the reaction mixture was stirred at room temperature for 17 hours. Subsequently, water (150 mL) was added to the reaction mixture, and the resultant mixture was extracted with ethyl acetate (150 mL×2). The organic layers were combined and washed with saturated brine (150 mL), followed by drying with sodium sulfate anhydrate. After filtration, the filtrate was concentrated under reduced pressure. The residue was dissolved in dimethylformamide (8 mL). Potassium carbonate (898 mg, 6.50 mmol) was added thereto under stirring while cooling with ice, and the resultant mixture was stirred at room temperature for 3 hours. The reaction mixture was cooled with ice, and 1N aqueous hydrochloric acid (15 mL) and water (30 mL) were added thereto, followed by stirring at room temperature for 2 hours. The solid matter that precipitated was collected through filtration and washed with water and a small amount of ethanol, to thereby yield the title compound as a pale yellow solid (890 mg, 82%).

1. concentrationThe reaction mixture was concentrated under reduced pressure and co-boiled with toluene (5 mL×3)
2. dissolutionThe residue was dissolved in dichloromethane (20 mL)
3. additionAfter completion of dropwise addition
4. stirringthe reaction mixture was stirred at room temperature for 17 hours
5. extractionthe resultant mixture was extracted with ethyl acetate (150 mL×2)
6. washwashed with saturated brine (150 mL)
7. dry with materialby drying with sodium sulfate anhydrate
8. filtrationAfter filtration
9. concentrationthe filtrate was concentrated under reduced pressure
10. dissolutionThe residue was dissolved in dimethylformamide (8 mL)
11. stirringunder stirring
12. temperaturewhile cooling with ice
13. additionwere added
14. stirringby stirring at room temperature for 2 hours
15. customThe solid matter that precipitated
16. filtrationwas collected through filtration
17. washwashed with water

ORD record

ord-5b38a233a24c42f981bcc07fa254eaed

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07723524B2