Hydrochloric Acid → HCID 86702140, compound

HRID 1776202Notes

Reaction equation

HRID 1776202 reaction equation
CC(C)([O-])C.[Na+].Cl[C:8]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.Cl>C([O-])(=O)C.C([O-])(=O)C.[Pd+2].O1CCOCC1>[F:22][C:19]1[CH:20]=[CH:21][C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][C:9]=2[CH:18]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 23676156Sodium t-butoxideHCID 86702139HCID 86702139, compound

Product 1

HCID 86702140HCID 86702140, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of sodium tert-butoxide (11.429 g, 118.9 mmol), 2-chloro-5-fluoro-N-(4-fluorophenyl)aniline (5.700 g, 23.8 mmol) and anhydrous 1,4-dioxane (120 mL) was degassed and back-filled with argon. Tri-tert-butylphosphonium tetrafluoroborate (0.483 g, 1.7 mmol) and palladium diacetate (0.267 g, 1.2 mmol) were added and the mixture was stirred in an oil bath at 110° C. for 20 hrs. After cooling to room temperature, the mixture was treated with 2M aqueous hydrochloric acid (90 mL) and extracted with methylene chloride (3×50 mL). The combined organic layers were washed with saturated aqueous sodium chloride, dried (anhydrous sodium sulfate), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (20-50% methylene chloride/hexanes). The solids were rinsed with hexanes and dried to afford the pure compound as a white powder (0.80 g, 17%). 1H NMR (300 MHz, CDCl3) δ 8.05 (br s, 1H), 7.94 (dd, 1H, J=8.7, 5.7 Hz), 7.67 (dd, 1H, J=8.7, 2.7 Hz), 7.35 (dd, 1H, J=9.0, 4.5 Hz), 7.14 (td, 1H, J=9.0, 2.7 Hz), 7.11 (dd, 1H, J=9.3, 2.4 Hz), 6.98 (ddd, 1H, J=9.3, 8.4, 2.4 Hz).

Workup

  1. customwas degassed
  2. additionback-filled with argon
  3. temperatureAfter cooling to room temperature
  4. extractionextracted with methylene chloride (3×50 mL)
  5. washThe combined organic layers were washed with saturated aqueous sodium chloride
  6. dry with materialdried (anhydrous sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (20-50% methylene chloride/hexanes)
  10. washThe solids were rinsed with hexanes
  11. customdried

Sources & evidence

ORD record
ord-14f8af99f64d41e182f15f546225fc47
Source dataset
uspto-grants-2016_02
Patent number
US09265772B2

Reaction notes

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