Diisobutylaluminumhydride → (3-iodo-1-isopropyl-1H-pyrazol-4-yl)methanol

Temperature

-78 °C

A solution of ethyl 3-iodo-1-isopropyl-1H-pyrazole-4-carboxylate (740 mg, 2.40 mmol) in tetrahydrofuran (20 mL) was cooled to −78° C. and treated with diisobutylaluminum hydride (1.5 M in toluene, 0.8 mL, 7.21 mmol), dropwise. The mixture was stirred at −78° C. for 1 hour and then warmed to room temperature for 2 hours. The mixture was quenched with 10 mL ethyl acetate, stirred 15 minutes, and then treated with 25 mL saturated aqueous Rochelle's salts. After stirring an additional 1 hour at room temperature, the mixture was diluted with 50 mL ethyl acetate and washed with 100 mL water. The aqueous layer was extracted with an additional 50 mL ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was then purified by flash chromatography (12-100% ethyl acetate/heptanes, 25 g silica gel) to yield 630 mg of (3-iodo-1-isopropyl-1H-pyrazol-4-yl)methanol as a clear oil. +APCI (M+H) 266.8; 1H NMR (400 MHz, CDCl3, δ): 7.37 (s, 1H), 4.49 (m, 3H), 1.67 (t, J=5.9 Hz, 1H), 1.50 (s, 6H).

1. temperaturewarmed to room temperature for 2 hours
2. customThe mixture was quenched with 10 mL ethyl acetate
3. stirringstirred 15 minutes
4. additiontreated with 25 mL saturated aqueous Rochelle's salts
5. stirringAfter stirring an additional 1 hour at room temperature
6. additionthe mixture was diluted with 50 mL ethyl acetate
7. washwashed with 100 mL water
8. extractionThe aqueous layer was extracted with an additional 50 mL ethyl acetate
9. dry with materialThe combined organic layers were dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was then purified by flash chromatography (12-100% ethyl acetate/heptanes, 25 g silica gel)

ORD record

ord-bb626221908b47a0aa5757196801d318

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08993586B2