Hydrochloric Acid → 4-chloro-1-(4-methoxy-2,6-dimethylphenyl)-1H-pyrazole

Temperature

-78 °C

To a −78° C. solution of Intermediate (79) (500 mg, 2.34 mmol) in THF (10 mL) was added n-BuLi (0.98 mL of a 2.5M solution in hexanes, 2.45 mmol). The reaction mixture was stirred for 30 min at −78° C. Di-t-butyl diazene-1,2-dicarboxylate (565 mg, 2.45 mmol) was added in one portion. The reaction mixture was allowed to warm to room temperature and stirred for 30 min. A solution of 2-chloromalonaldehyde (260 mg, 2.45 mmol) in THF (2.0 mL) was added dropwise at 0° C. 4M HCl in dioxane (10 mL) was added. The reaction mixture was stirred at reflux overnight. Saturated aqueous NaHCO3 was added to bring the aqueous layer to pH=7. The mixture was extracted with ethyl acetate (10 ml×3). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography to give compound 4-chloro-1-(4-methoxy-2,6-dimethylphenyl)-1H-pyrazole (100 mg) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.57 (s, 1H), 7.35 (s, 1H), 6.57 (s, 2H), 3.74 (s, 3H), 1.92 (s, 6H).

1. temperatureto warm to room temperature
2. stirringstirred for 30 min
3. stirringThe reaction mixture was stirred
4. temperatureat reflux overnight
5. extractionThe mixture was extracted with ethyl acetate (10 ml×3)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. concentrationconcentrated under reduced pressure
8. customThe crude residue was purified by silica gel chromatography

ORD record

ord-2c86866926b240d2b215add4d507b5eb

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507533B2