HCID 59703982, compound → HCID 44182379, compound

HRID 1850003Notes

Reaction equation

HRID 1850003 reaction equation
Br[C:2]([CH3:16])([CH3:15])[C:3]([NH:5][C:6]1[O:10][N:9]=[C:8]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:7]=1)=[O:4].[F:17][C:18]([F:27])([F:26])[C:19]1[CH:20]=[CH:21][C:22]([OH:25])=[N:23][CH:24]=1>C(#N)C.O.[Ag-]=O>[C:11]([C:8]1[CH:7]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:16])([O:25][C:22]2[CH:21]=[CH:20][C:19]([C:18]([F:26])([F:17])[F:27])=[CH:24][N:23]=2)[CH3:15])[O:10][N:9]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

5

Reactant 2

HCID 59703982HCID 59703982, compoundHCID 178516044HCID 178516044, compound

Product 1

HCID 44182379HCID 44182379, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 178418778HCID 178418778, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-bromo-N-(3-tert-butyl-isoxazol-5-yl)-2-methyl-propionamide (0.53 g, 1.78 mmol) and 5-trifluoromethyl-2-pyridinol (0.30 g, 1.84 mmol) in acetonitrile/water (95/5, 15 mL) is added silver (I) oxide (0.85 g, 3.68 mmol). The reaction is heated to 60° C. for 18 h. After cooling, the reaction mixture is filtered through a plug of Na2SO4/cotton wool. The filtrate is concentrated under reduced pressure to give a brown oil, which is triturated with heptanes/ethyl acetate to afford a grey powder. Further purification by column chromatography (silica, eluent heptanes, 2.5-20% ethyl acetate) afforded N-(3-tert-butyl-isoxazol-5-yl)-2-methyl-2-(5-trifluoromethyl-pyridin-2-yloxy)-propionamide as a white solid (33 mg, 5%). m/z 372 [M+H+]

Workup

  1. temperatureAfter cooling
  2. filtrationthe reaction mixture is filtered through a plug of Na2SO4/cotton wool
  3. concentrationThe filtrate is concentrated under reduced pressure
  4. customto give a brown oil, which
  5. customis triturated with heptanes/ethyl acetate
  6. customto afford a grey powder
  7. customFurther purification by column chromatography (silica, eluent heptanes, 2.5-20% ethyl acetate)

Sources & evidence

ORD record
ord-1609bacb989c439187a2e72b9f3fc156
Source dataset
uspto-grants-2015_02
Patent number
US08957063B2

Reaction notes

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