Sodium Hydroxide → (5-Bromo-1-isopropyl-1H-pyrazol-4-YL)methanol

To a solution of ethyl 5-bromo-1-isopropyl-1H-pyrazole-4-carboxylate (163 g, 0.50 mol) in 2-methyl tetrahydrofuran (400 mL) was added borane-DMS (140 mL, 1.50 mol) at 0° C., under argon (effervescence ceased after 50 mL was added). The mixture was stirred at room temperature for 30 minutes and then heated to 70° C. for 2 hours, and then to reflux for 17 hours. Additional portion of borane DMS (40 mL) was added and the mixture was stirred at reflux for an additional 3 hours. The mixture was cooled to room temperature then added gradually to ice-cold methanol (500 mL) with stirring, over a period of 30 minutes. The mixture was stirred at room temperature for 30 minutes then 2 M aqueous sodium hydroxide (1.5 L) was added. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×500 mL). The organic layers were combined, washed with brine (500 mL), dried over magnesium sulfate, filtered and the solvent removed in vacuo. The crude product was purified by dry flash chromatography (0-50% ethyl acetate in heptane) to give (5-bromo-1-isopropyl-1H-pyrazol-4-yl)methanol (70.8 g, 65% over two steps). +ESI (M+H) 220.9; 1H NMR (400 MHz, CDCl3, δ): 7.52 (s, 1H), 4.67 (m, 1H), 4.47 (s, 2H), 2.59 (br. s., 1H), 1.41 (s, 6H).

1. temperatureheated to 70° C. for 2 hours
2. temperatureto reflux for 17 hours
3. stirringthe mixture was stirred
4. temperatureat reflux for an additional 3 hours
5. temperatureThe mixture was cooled to room temperature
6. stirringwith stirring, over a period of 30 minutes
7. stirringThe mixture was stirred at room temperature for 30 minutes
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with ethyl acetate (2×500 mL)
10. washwashed with brine (500 mL)
11. dry with materialdried over magnesium sulfate
12. filtrationfiltered
13. customthe solvent removed in vacuo
14. customThe crude product was purified
15. dry with materialby dry flash chromatography (0-50% ethyl acetate in heptane)

ORD record

ord-27d9f055a32d49958b9ac48de964e6f9

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181252B2