HCID 178524578, compound → HCID 178526711, compound

Temperature

-5 °C

A 3-L three-neck round-bottomed flask equipped with a mechanical stirrer, addition funnel and nitrogen inlet was purged with nitrogen and charged with 3-nitropyrazole-5-carboxylic acid (28.0 g, 178 mmol) and THF (420 mL) and cooled to −5° C. using an ice/acetone bath. Borane-THF complex solution (1.0 M, 535 mL, 535 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 room temperature for 18 h. After this time the reaction was cooled to −5° C. using an ice/acetone bath, water (70 mL) and 4N hydrochloric acid (70 mL) was added and the reaction was stirred at reflux for 1 h in order to destroy the borane complex with pyrazole. The reaction was cooled to room temperature and concentrated under reduced pressure to a volume of approximately 30 mL. Ethyl acetate (175 mL) was added and the mixture stirred for 15 min. The aqueous layer was separated and extracted with ethyl acetate (4×200 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate (2×50 mL), brine (50 mL) and dried over sodium sulfate, the drying agent was removed by filtration, and the filtrate concentrated under reduced pressure to afford 125a in a 94% yield (24.0 g) as a light yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 13.90 (br s, 1H), 6.87 (s, 1H), 5.58 (t, 1H, J=5.4 Hz), 4.53 (d, 2H, J=5.1 Hz); MS (ESI+) m/z 144.0 (M+H)

1. customA 3-L three-neck round-bottomed flask equipped with a mechanical stirrer, addition funnel and 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 (70 mL) and 4N hydrochloric acid (70 mL) was added
8. stirringthe reaction was stirred
9. temperatureat reflux for 1 h in order
10. customto destroy the borane complex with pyrazole
11. temperatureThe reaction was cooled to room temperature
12. concentrationconcentrated under reduced pressure to a volume of approximately 30 mL
13. additionEthyl acetate (175 mL) was added
14. stirringthe mixture stirred for 15 min
15. customThe aqueous layer was separated
16. extractionextracted with ethyl acetate (4×200 mL)
17. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate (2×50 mL), brine (50 mL)
18. dry with materialdried over sodium sulfate
19. customthe drying agent was removed by filtration
20. concentrationthe filtrate concentrated under reduced pressure

ORD record

ord-367ca392a41942e9ace9cc76cbf1bce5

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921353B2