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

HRID 1180631Notes

Reaction equation

HRID 1180631 reaction equation
[CH3:1][N:2]1[C:6](OS(C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)(=O)=O)=[CH:5][C:4]([Br:24])=[N:3]1.[F:25][C:26]([F:37])([F:36])[C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>CN(C)C=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][N:2]1[C:6]([C:30]2[CH:31]=[CH:32][C:27]([C:26]([F:37])([F:36])[F:25])=[CH:28][CH:29]=2)=[CH:5][C:4]([Br:24])=[N:3]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 117755091-Methyl-3-bromo-5-(nonafluorobutanesulfonyloxy)pyrazole

Product 1

HCID 221479921-Methyl-3-bromo-5-(4-trifluoromethylphenyl)pyrazoleYield 56.2%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

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

Workup

  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

Sources & evidence

ORD record
ord-dc2bf413c69344ed8dfc9f219a2c5591
Source dataset
uspto-grants-2007_10
Patent number
US07282513B2

Reaction notes

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