Water → HCID 86684911, compound

HRID 2402906Notes

Reaction equation

HRID 2402906 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][C:11]([NH2:13])=[O:12])=[C:4]([C:14]([F:17])([F:16])[F:15])[CH:3]=1.[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O.COC(C)(C)C>[CH3:18][N:19]1[CH:23]=[C:22]([C:2]2[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][C:11]([NH2:13])=[O:12])=[C:4]([C:14]([F:17])([F:16])[F:15])[CH:3]=2)[CH:21]=[N:20]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86684910HCID 86684910, compound

Product 1

HCID 86684911HCID 86684911, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
50 °C

Procedure

3-(4-Bromo-2-trifluoromethyl-phenylsulfanyl)-propionamide (160 g, 488 mmol) was dissolved under Ar in N,N-dimethylformamide (1.5 L) before 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (143 g, 687 mmol), potassium carbonate (160 g, 1.16 mol), and water (130 mL) were added. The solution was degassed and tetrakis-(triphenylphosphine)palladium(0) (24.0 g, 20.8 mmol) was added. The mixture was stirred for 16 h at 50° C. After cooling to room temperature, the mixture was poured onto water (5 L) and extracted with ethyl acetate (1×3 L, 2×1 L). The combined organic extracts were washed with brine (1 L), the volume was reduced in vacuo to ca. 2 L and dried over sodium sulfate. The resulting filtrate was further reduced in vacuo until precipitation occurred and a homogeneous slurry was formed. Tert-butyl methyl ether (1 L) was then added in portions to the distillation, keeping the overall volume constant (solvent exchange). The suspension was cooled to 5° C. (ice bath) and filtered. The precipitate was washed with tert-butyl methyl ether (500 mL) and dried in vacuo to provide 141 g of the title compound as brown crystalline solid (88%). MS (ESI & APCI): m/z=330.1 [M+H]. 1H NMR (CDCl3, 600 MHz): δ 2.54 (t, J=7.4 Hz, 2H), 3.27 (t, J=7.4 Hz, 2H), 5.39 (bs, 1H), 5.52 (bs, 1H), 7.56 (s, 1H), 7.57 (s, 1H), 7.66 (s, 1H), 7.73 (bs, 1H), 7.77 (d, J=0.7 Hz, 1H).

Workup

  1. additionwere added
  2. customThe solution was degassed
  3. temperatureAfter cooling to room temperature
  4. additionthe mixture was poured onto water (5 L)
  5. extractionextracted with ethyl acetate (1×3 L, 2×1 L)
  6. washThe combined organic extracts were washed with brine (1 L)
  7. dry with materialdried over sodium sulfate
  8. customThe resulting filtrate was further reduced in vacuo until precipitation
  9. customa homogeneous slurry was formed
  10. temperatureThe suspension was cooled to 5° C. (ice bath)
  11. filtrationfiltered
  12. washThe precipitate was washed with tert-butyl methyl ether (500 mL)
  13. customdried in vacuo

Sources & evidence

ORD record
ord-b028d96ec03341b6ac77a5ace496c547
Source dataset
uspto-grants-2014_08
Patent number
US08796471B2

Reaction notes

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