Hexachloroethane → 5-Chloro-3-(2,5-dimethyl-1H-pyrrol-1-yl)-1-methyl-1H-pyrazole

Temperature

-70 °C

A solution of 3-(2,5-dimethyl-pyrrol-1-yl)-1-methyl-1H-pyrazole (Intermediate 7, 0.51 g, 2.91 mmol) in tetrahydrofuran (25 mL) cooled to −70° C. was treated dropwise with a 2.5M solution of n-butyllithium in hexanes (1.3 mL, 3.25 mmol). The reaction was stirred at −70° C. for 2.6 h. After this time, the reaction was treated dropwise over 2-3 min with a solution of hexachloroethane (0.77 g, 3.2 mmol) in tetrahydrofuran (2.5 mL). The reaction was maintained at −70° C. for 20-25 min. After this time, the cooling bath was removed. The reaction continued to stir for 90 min, at which time the reaction was concentrated in vacuo. The residue was then partitioned between water (50 mL) and diethyl ether (1×50 mL). The organics were washed with a saturated aqueous sodium chloride solution (1×50 mL), dried over magnesium sulfate, filtered, rinsed with diethyl ether and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 40 g, 5-10% ethyl acetate/hexanes) afforded 5-chloro-3-(2,5-dimethyl-pyrrol-1-yl)-1-methyl-1H-pyrazole (0.36 g, 60%) as a light brown solid; ES+-HRMS m/e calcd for C10H12N3Cl [M+H+] 210.0793, found 210.0792.

1. temperatureThe reaction was maintained at −70° C. for 20-25 min
2. customAfter this time, the cooling bath was removed
3. stirringto stir for 90 min, at which time the reaction
4. concentrationwas concentrated in vacuo
5. customThe residue was then partitioned between water (50 mL) and diethyl ether (1×50 mL)
6. washThe organics were washed with a saturated aqueous sodium chloride solution (1×50 mL)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. washrinsed with diethyl ether
10. concentrationconcentrated in vacuo

ORD record

ord-c24e618bbb2b45b187b4cce5040b5a56

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258134B2