Potassium Phosphate, Tribasic → HCID 57706268, compound

HRID 404372Notes

Reaction equation

HRID 404372 reaction equation
[CH3:1][C:2]1([CH3:26])[C:6]([C:7]2[CH:8]=[C:9]([CH:14]=[C:15]([F:25])[C:16]=2OS(C(F)(F)F)(=O)=O)[C:10]([O:12][CH3:13])=[O:11])=[CH:5][CH2:4][CH2:3]1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[F:56][C:57]1[CH:62]=[CH:61][C:60]([O:63][CH3:64])=[CH:59][C:58]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:26][C:2]1([CH3:1])[C:6]([C:7]2[CH:8]=[C:9]([C:10]([O:12][CH3:13])=[O:11])[CH:14]=[C:15]([F:25])[C:16]=2[C:58]2[CH:59]=[C:60]([O:63][CH3:64])[CH:61]=[CH:62][C:57]=2[F:56])=[CH:5][CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57706468HCID 57706468, compound

Product 1

HCID 57706268HCID 57706268, compoundYield 95%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A stirred mixture of T33.6 (0.9464 g, 2.39 mmol), ground S-Phos (0.1977 g, 0.482 mmol), palladium acetate (0.0555 g, 0.247 mmol), 2-fluoro-5-methoxyphenylboronic acid (0.8114 g, 4.77 mmol) (commercially available from Sigma-Aldrich, St. Louis, Mo., USA), and potassium phosphate tribasic (1.2888 g, 6.072 mmol) in dry DMF (7.000 mL) was purged with argon and placed under vacuum and the process repeated three times. The mixture was then heated to 75° C. and the reaction was stirred for 21 hours. The reaction was then cooled to room temperature, diluted with water and extracted three times with EtOAc. The organic layers were combined and washed twice with brine. After drying over anhydrous sodium sulfate and filtration, the organic solvent was removed under reduced pressure. The residue was purified on an 80 g column of silica gel (0-20% EtOAc in hexanes) to afford T33.7 as a colorless oil that was used without further purification (850.5 mg, 95% yield). MS ESI (pos.) m/e: 373.0 (M+H)+.

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. extractionextracted three times with EtOAc
  3. washwashed twice with brine
  4. dry with materialAfter drying over anhydrous sodium sulfate and filtration
  5. customthe organic solvent was removed under reduced pressure
  6. customThe residue was purified on an 80 g column of silica gel (0-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8e35141c3cb4410e974187514c37a065
Source dataset
uspto-grants-2014_06
Patent number
US08748462B2

Reaction notes

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