Triethylamine → HCID 68502348, compound

HRID 888361Notes

Reaction equation

HRID 888361 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][C:9]=2[F:15])[CH:7]=1.[CH3:20][CH2:21]N(CC)CC>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCO>[F:15][C:9]1[CH:10]=[C:11]([CH3:14])[CH:12]=[CH:13][C:8]=1[C:6]1[CH:7]=[C:2]([CH:20]=[CH2:21])[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[CH:5]=1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 68499851Methyl 5-bromo-2'-fluoro-4'-methylbiphenyl-3-carboxylate

Product 1

HCID 68502348HCID 68502348, compoundYield 693.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolvent

Conditions

Temperature
140 °C

Procedure

To Biotage Advancer MW reactor was charged methyl 5-bromo-2′-fluoro-4′-methylbiphenyl-3-carboxylate (20 g, 61.9 mmol), PdCl2(dppf) (0.20 g, 0.273 mmol), potassium vinyl trifluoroborate (12.4 g, 93 mmol), Et3N (13.0 ml, 93 mmol) and EtOH (150 ml). The reactor was sealed and heated at 140° C. for 10 min followed by flash cooling. Removed mixture from the cooling reservoir via vacuum and reaction repeated 5× (120 g, 371 mmol processed). All runs were combined and concentrated to dryness. The crude was partitioned between water and dichloromethane. The layers were separated and the aqueous extracted 2× w/DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated via rotary evaporation to give 116 g amber oil. The crude was purified by automated silica gel chromatography (750 g SiO2, EtOAc/hexanes) to give nearly colorless oil which solidified to white solid upon cooling (99.7 g, 99%).

Workup

  1. customThe reactor was sealed
  2. temperaturecooling
  3. customRemoved mixture from the cooling reservoir
  4. customvia vacuum and reaction
  5. concentrationconcentrated to dryness
  6. customThe crude was partitioned between water and dichloromethane
  7. customThe layers were separated
  8. extractionthe aqueous extracted 2× w/DCM
  9. dry with materialThe combined organic layers were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated via rotary evaporation

Sources & evidence

ORD record
ord-27529e07d86a4f52af94ab730c30f398
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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