Hydrochloric Acid → HCID 57787301, compound

HRID 2426780Notes

Reaction equation

HRID 2426780 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH2:5][O:6][C:7]1[CH:20]=[CH:19][C:10]([CH2:11][N:12]2[C:16](=[O:17])[NH:15][C:14](=[O:18])[O:13]2)=[CH:9][CH:8]=1.[F:24][C:25]1[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[C:27]([F:33])[C:26]=1B(O)O.[Cl-].[Li+].C(=O)([O-])[O-].[Na+:43].[Na+].Cl.[OH-].[Na+]>C1COCC1.C(O)C.COCCOC>[F:24][C:25]1[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[C:27]([F:33])[C:26]=1[C:2]1[CH:23]=[CH:22][CH:21]=[C:4]([CH2:5][O:6][C:7]2[CH:20]=[CH:19][C:10]([CH2:11][N:12]3[C:16](=[O:17])[N-:15][C:14](=[O:18])[O:13]3)=[CH:9][CH:8]=2)[CH:3]=1.[Na+:43]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 433294Lithium ChlorideHCID 162174242,6-Difluoro-4-methoxybenzeneboronic acid4×HCID 57787607HCID 57787607, compound

Product 1

HCID 57787301HCID 57787301, compoundYield 59.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-{4-[(3-bromobenzyl)oxy]benzyl}-1,2,4-oxadiazolidine-3,5-dione (500 mg), 2,6-difluoro-4-methoxyphenyl boronic acid (325 mg), tetrakistriphenylphosphine palladium (80 mg), lithium chloride (6 mg), a sodium carbonate aqueous solution (562 mg/5 ml), ethanol (5 ml) and 1,2-dimethoxyethane (25 ml) was stirred at 90° C. for 5 hours in an atmosphere of nitrogen. 2,6-Difluoro-4-methoxyphenyl boronic acid (325 mg) was further added thereto, followed by stirring at 90° C. for 13 hours. Further, 2,6-difluoro-4-methoxyphenyl boronic acid (325 mg) was added thereto, followed by stirring at 90° C. for 2 hours. Further, 2,6-difluoro-4-methoxyphenyl boronic acid (325 mg) was added thereto, followed by stirring at 90° C. for 5 hours and spontaneous cooling to room temperature. A 1 M hydrochloric acid (50 ml) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and then dried over anhydrous magnesium sulfate and filtered. Silica gel (3 g) was added to the filtrated, followed by concentration under a reduced pressure. The carrying product thus obtained was purified by silica gel column chromatography (chloroform-methanol) to obtain a light yellow foamy substance (614 mg). The resulting foamy substance (614 mg) was dissolved in THF (5 ml)-ethanol (5 ml), a 1 M sodium hydroxide aqueous solution (1.32 ml) was added, followed by concentration under a reduced pressure. By recrystallizing the resulting residue from isopropanol-water, sodium 2-{4-[(2′,6′-difluoro-4′-methoxybiphenyl-3-yl)methoxy]benzyl}-3,5-dioxo-1,2,4-oxadiazolidin-4-ide (366 mg) was obtained as a colorless solid.

Workup

  1. stirringby stirring at 90° C. for 2 hours
  2. stirringby stirring at 90° C. for 5 hours
  3. temperaturespontaneous cooling to room temperature
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. additionSilica gel (3 g) was added to the filtrated
  9. concentrationfollowed by concentration under a reduced pressure
  10. customThe carrying product thus obtained
  11. customwas purified by silica gel column chromatography (chloroform-methanol)
  12. customto obtain a light yellow foamy substance (614 mg)
  13. concentrationfollowed by concentration under a reduced pressure
  14. customBy recrystallizing the resulting residue from isopropanol-water

Sources & evidence

ORD record
ord-012c31b6ed9b4046a5f3e665c4177205
Source dataset
uspto-grants-2011_06
Patent number
US07968552B2

Reaction notes

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