HCID 178524578, compound → HCID 178526711, compound

Temperature

-5 °C

A 100-mL three-neck round-bottomed flask equipped with a nitrogen inlet was purged with nitrogen and charged with 3-nitropyrazole-5-carboxylic acid (0.56 g, 3.56 mmol) and THF (8 mL). The system was cooled to −5° C. using an ice/acetone bath. Borane-THF complex solution (1.0M, 11 mL, 11.0 mmol) was added at a rate that maintained the internal reaction temperature below 5° C. After the addition was complete the cooling bath was removed and the reaction was stirred at 60° C. for 3 h. After this time the reaction was cooled to −5° C. using an ice/acetone bath, water (2 mL) and 4N hydrochloric acid (2 mL) was added. The reaction mixture was stirred at 70° C. for 1 h in order to destroy the borane-pyrazole complex. It was cooled to room temperature and concentrated under reduced pressure to a volume of approximately 1 mL. Ethyl acetate (20 mL) and water (10 mL) were added and the mixture was stirred for 15 min. The aqueous layer was separated and extracted with ethyl acetate (4×10 mL). The combined organic layer was washed with saturated aqueous sodium bicarbonate (2×10 mL), brine (10 mL), and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure to afford 296a (345 mg, 68%) as a light yellow solid. MS-ESI: [M+H]+ 144

1. customA 100-mL three-neck round-bottomed flask equipped with a nitrogen inlet
2. customwas purged with nitrogen
3. temperaturemaintained the internal reaction temperature below 5° C
4. additionAfter the addition
5. customwas removed
6. temperatureAfter this time the reaction was cooled to −5° C.
7. additionwater (2 mL) and 4N hydrochloric acid (2 mL) was added
8. stirringThe reaction mixture was stirred at 70° C. for 1 h in order
9. customto destroy the borane-pyrazole complex
10. temperatureIt was cooled to room temperature
11. concentrationconcentrated under reduced pressure to a volume of approximately 1 mL
12. additionEthyl acetate (20 mL) and water (10 mL) were added
13. stirringthe mixture was stirred for 15 min
14. customThe aqueous layer was separated
15. extractionextracted with ethyl acetate (4×10 mL)
16. washThe combined organic layer was washed with saturated aqueous sodium bicarbonate (2×10 mL), brine (10 mL)
17. dry with materialdried over sodium sulfate
18. customThe drying agent was removed by filtration
19. concentrationthe filtrate was concentrated under reduced pressure

ORD record

ord-dd37cb4deae3494f905220f29fb56d96

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716274B2