Hydrochloric Acid → 1-Methyl-3-bromo-5-(4-trifluoromethylphenyl)pyrazole

A solution of 1-methyl-3-bromo-5-(nonafluorobutanesulfonyloxy)pyrazole from Example 69 Step 2 (0.16 g, 0.35 mmol), 4-trifluoromethylbenzeneboronic acid (0.07 g, 0.36 mmol), tetrakis(triphenylphosphine) palladium (0) (0.04 g, 10 mol %), sodium carbonate (0.04 g, 0.38 mmol) in dry N,N-dimethylformamide (2 mL) was stirred under nitrogen at 40° C. for 18 hours. The cooled reaction mixture was poured into 1M hydrochloric acid (10 ml) and extracted with diethyl ether (2×10 mL). The combined organic layers were dried (Na2SO4) and concentrated to give an oil which was purified by flash column chromatography on silica eluting with 5% ethyl acetate—isohexane to give 1-methyl-3-bromo-5-(4-trifluoromethylphenyl)pyrazole as a white solid (0.06 g, 56%). δ (1H, 400 MHz, CDCl3) 3.86 (3H, s), 6.37 (1H, s), 7.53 (2H, d, J=8 Hz), 7.74 (2H, d, J=8 Hz). Step 2: [6S,9R,11R] 2′,3′,4′,5,5′,6,7,8,9,10-decahydro-2-(5-(4-trifluoromethylphenyl)-1-methyl-pyrazol-3-yl)-5′-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3′-[1,2,5]thiadiazole] 1′,1′-dioxide

1. customThe cooled reaction mixture
2. extractionextracted with diethyl ether (2×10 mL)
3. dry with materialThe combined organic layers were dried (Na2SO4)
4. concentrationconcentrated
5. customto give an oil which
6. customwas purified by flash column chromatography on silica eluting with 5% ethyl acetate—isohexane

ORD record

ord-dc2bf413c69344ed8dfc9f219a2c5591

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07282513B2