Potassium Phosphate, Tribasic → N-(2-Bromo-5-cyano-3-methoxy-6-methylbiphenyl-4-yl)2,2,2-trifluoroacetamide

HRID 17295Notes

Reaction equation

HRID 17295 reaction equation
[Br:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]([NH:12][C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[C:5]([C:10]#[N:11])=[C:6]([CH3:9])[C:7]=1I.[C:21]1(B2OCCCO2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.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>[Br:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]([NH:12][C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[C:5]([C:10]#[N:11])=[C:6]([CH3:9])[C:7]=1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 642685Phenylboronic acid 1,3-propanediol esterHCID 86630812N-(3-Bromo-6-cyano-4-iodo-2-methoxy-5-methylphenyl)-2,2,2-trifluoroacetamide

Product 1

HCID 86630811N-(2-Bromo-5-cyano-3-methoxy-6-methylbiphenyl-4-yl)2,2,2-trifluoroacetamideYield 84%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

N-(3-Bromo-6-cyano-4-iodo-2-methoxy-5-methylphenyl)-2,2,2-trifluoroacetamide (I-36) (1.29 g, 2.79 mmol), 2-phenyl-1,3,2-dioxaborinane (474 mg, 2.93 mmol), tripotassium phosphate (74-85%, 1.48 g, 5.58 mmol) and tetrakis(triphenylphosphine)palladium(0) (406 mg, 0.352 mmol) were added to a 30-ml eggplant-type flask, followed by purging with nitrogen, N,N-dimethylformamide (50 ml) was injected into it with a syringe, followed by stirring overnight at 95° C. After cooling, the reaction liquid was diluted with ethyl acetate, successively washed with saturated brine (×3), 1 N hydrochloric acid, saturated brine, an aqueous saturated sodium hydrogencarbonate solution and saturated brine. The organic layer was dried on anhydrous magnesium sulfate, then the solvent was concentrated under reduced pressure to obtain a brown residue. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1) to obtain the entitled compound (968 mg, 84%) as a brown solid.

Workup

  1. customby purging with nitrogen, N,N-dimethylformamide (50 ml)
  2. customwas injected into it with a syringe
  3. temperatureAfter cooling
  4. customthe reaction liquid
  5. washsuccessively washed with saturated brine (×3), 1 N hydrochloric acid, saturated brine
  6. dry with materialThe organic layer was dried on anhydrous magnesium sulfate
  7. concentrationthe solvent was concentrated under reduced pressure
  8. customto obtain a brown residue
  9. customThe resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1)

Sources & evidence

ORD record
ord-72d69f230e264b3a86a37e6c8ea13a17
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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