Lithium borohydride → (1-methyl-3-nitro-1H-pyrazol-5-yl)methanol

Temperature

0 °C

A 100-mL three-neck round-bottomed flask equipped with a magnetic stirrer, addition funnel and nitrogen inlet was purged with nitrogen and charged with 156b (0.67 g, 3.6 mmol), THF (20 mL) and cooled to 0° C. using an ice bath. 2 M lithium borohydride solution (3.6 mL, 7.2 mmol) was added dropwise 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 3 h. The reaction was cooled to 0° C. using an ice bath, and saturated aqueous sodium bicarbonate (30 mL) was added dropwise. The layers were separated, and aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine (30 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, ethyl acetate/hexanes) to afford a quant. yield (0.56 g) of (1-methyl-3-nitro-1H-pyrazol-5-yl)methanol (156c) as an off-white solid: MS (ESI+) m/z 158.1 (M+H).

1. customA 100-mL three-neck round-bottomed flask equipped with a magnetic 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. customthe cooling bath was removed
6. temperatureThe reaction was cooled to 0° C.
7. additionsaturated aqueous sodium bicarbonate (30 mL) was added dropwise
8. customThe layers were separated
9. extractionaqueous layer was extracted with ethyl acetate (3×30 mL)
10. washThe combined organic layers were washed with brine (30 mL)
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated under reduced pressure
13. customThe residue was purified by column chromatography (silica, ethyl acetate/hexanes)

ORD record

ord-4fbb80bc71c147e2a51db4b7e57a5c0d

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618107B2