Sodium Carbonate → HCID 69093177, compound

HRID 918888Notes

Reaction equation

HRID 918888 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1B(O)O.[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+].[CH3:20][CH2:21][O:22][C:23]([CH3:25])=[O:24].O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:2]1[CH2:3][CH2:4][C:23]2([O:24][CH2:20][CH2:21][O:22]2)[CH2:25][CH:7]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343342,4-Difluorophenylboronic acidHCID 22728543Water ethylacetate

Product 1

HCID 69093177HCID 69093177, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A mixture of intermediate I-25 (6.11 g, 89% pure, 18.86 mmol), 2,4-difluorophenyl-boronic acid (4.55 g, 28.86 mmol), LiCl (3.26 g, 1.41 mmol), Na2CO3 (8.1 g, 76.46 mmol), in DME (70.2 mL) and H2O (38 mL) was deoxygenated with a nitrogen flow. Then, tetrakis(triphenylphosphine)palladium (0) (1.63 g, 1.41 mmol) was added and the mixture was stirred under nitrogen atmosphere, at reflux for 5 hours. After cooling, the mixture was diluted with EtOAc/H2O and filtered off over diatomaceous earth. The filtrate was washed with saturated NaHCO3 and extracted with EtOAc. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by two flash column chromatographies (silica; EtOAc in heptane 0/100 to 5/95, then silica; CH2Cl2 100%). The desired fractions were collected and concentrated in vacuo to yield intermediate I-26 (1.56 g, 32.7%) as oil.

Workup

  1. customin DME (70.2 mL) and H2O (38 mL) was deoxygenated with a nitrogen flow
  2. temperatureat reflux for 5 hours
  3. temperatureAfter cooling
  4. filtrationfiltered off over diatomaceous earth
  5. washThe filtrate was washed with saturated NaHCO3
  6. extractionextracted with EtOAc
  7. customThe organic layer was separated
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customthe solvents evaporated in vacuo
  11. customThe crude product was purified by two flash column chromatographies (silica
  12. customThe desired fractions were collected
  13. concentrationconcentrated in vacuo
  14. customto yield intermediate I-26 (1.56 g, 32.7%) as oil

Sources & evidence

ORD record
ord-f0f09e79ce154d8f967205f68184c18c
Source dataset
uspto-grants-2016_03
Patent number
US09271967B2

Reaction notes

Loading…