Water → N-(5-cyano-2-fluoro-3-methoxy-6-methylbiphenyl-4-yl)-2,2,2-trifluoroacetamide

HRID 17294Notes

Reaction equation

HRID 17294 reaction equation
CN(C)C=O.[C:6]([C:8]1[C:13]([CH3:14])=[C:12](I)[C:11]([F:16])=[C:10]([O:17][CH3:18])[C:9]=1[NH:19][C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])#[N:7].[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.O>[Cl-].[Na+].O>[C:6]([C:8]1[C:9]([NH:19][C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])=[C:10]([O:17][CH3:18])[C:11]([F:16])=[C:12]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:13]=1[CH3:14])#[N:7]

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 66827Phenylboronic AcidHCID 86630809N-(2-Cyano-5-fluoro-4-iodo-6-methoxy-3-methylphenyl)-2,2,2-trifluoroacetamide

Product 1

HCID 86630810N-(5-cyano-2-fluoro-3-methoxy-6-methylbiphenyl-4-yl)-2,2,2-trifluoroacetamideYield 98%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

Under nitrogen atmosphere, tetrakistriphenylphosphine palladium(0) (288 mg, 0.25 mmol) was added to an N,N-dimethylformamide (15 ml) suspension of N-(2-cyano-5-fluoro-4-iodo-6-methoxy-3-methylphenyl)-2,2,2-trifluoroacetamide (I-35) (500 mg, 1.24 mmol), phenylboronic acid (228 mg, 1.87 mmol), potassium phosphate n-hydrate (890 mg, 3.1 mmol), followed by stirring with heating under reflux for 15 hours and a half. After cooling to room temperature, water and saturated brine were added to the reaction liquid, followed by extraction three times with ethyl acetate, the organic layer was washed with saturated ammonium chloride water, then dried over anhydrous magnesium sulfate. After filtration and concentration under reduced pressure, the resulting residue was subjected to column chromatography, and the eluate with n-hexane:ethyl acetate (5:1) was concentrated under reduced pressure to obtain the entitled compound (427 mg, 98%) as a white solid.

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 15 hours
  3. extractionfollowed by extraction three times with ethyl acetate
  4. washthe organic layer was washed with saturated ammonium chloride water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationAfter filtration and concentration under reduced pressure
  7. concentrationthe eluate with n-hexane:ethyl acetate (5:1) was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b3c45415330142778e895c612186cc75
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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