Potassium Phosphate, Tribasic → HCID 86674202, compound

HRID 241443Notes

Reaction equation

HRID 241443 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH:8]([F:10])[F:9])=[N:6][CH:7]=1.Cl.[CH3:12][NH:13]OC.C1(P(C2C=CC=CC=2)C2[C:36]3[O:35]C4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C:66](=[O:69])(O)[O-].[Na+]>C1(C)C=CC=C(C)C=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:9][CH:8]([F:10])[C:5]1[N:6]=[CH:7][C:2]([C:66]([N:13]([O:35][CH3:36])[CH3:12])=[O:69])=[CH:3][CH:4]=1

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 516892Sodium BicarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 534150625-Bromo-2-(difluoromethyl)pyridine

Product 1

HCID 86674202HCID 86674202, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7929M-XyleneSolvent

Conditions

Temperature
100 °C

Procedure

Combine 5-bromo-2-(difluoromethyl)pyridine (5.00 g, 24.03 mmol), N,O-dimethylhydroxylamine hydrochloride (3.52 g, 36.09 mmol), palladium(II) acetate (0.162 g, 0.722 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.695 g, 1.201 mmol), and potassium phosphate (tribasic) (15.3 g, 72.07 mmol) in m-xylene (50 mL). Purge the reaction vessel with carbon monoxide gas. Heat the solution to 100° C., and stir under an atmosphere of carbon monoxide for 16 hours. Safely purge the vessel in a well-ventilated area with nitrogen until it is free of carbon monoxide. Add water (200 mL) to quench the reaction. Adjust the pH of the mixture to 7 with a saturated sodium bicarbonate aqueous solution. Extract the mixture with EtOAc. Dry the combined organic extracts over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure. Purify the resulting residue by silica gel chromatography eluting with a 2:1 ratio of petroleum ether to EtOAc to give the title compound (2.5 g, 48% yield) as a clear oil. LCMS (m/z) 216 (M+1).

Workup

  1. customPurge the reaction vessel with carbon monoxide gas
  2. customSafely purge the vessel in a well-ventilated area with nitrogen until it
  3. customAdd water (200 mL) to quench
  4. customthe reaction
  5. extractionExtract the mixture with EtOAc
  6. dry with materialDry the combined organic extracts over sodium sulfate
  7. filtrationfilter
  8. customcollect the filtrate
  9. concentrationand concentrate the filtrate under reduced pressure
  10. customPurify the resulting residue by silica gel chromatography
  11. washeluting with a 2:1 ratio of petroleum ether to EtOAc

Sources & evidence

ORD record
ord-295886aa017040debcfd6842c3261a0e
Source dataset
uspto-grants-2014_02
Patent number
US08648200B2

Reaction notes

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