2,6-Di-tert-butyl-4-methylphenol → 2-Cyclopropyl-7-fluoro-5-methyl-6-(thiophen-2-yl)-1,3-benzoxazole-4-carbonitrile

HRID 17595

Reaction equation

HRID 17595 reaction equation
Br[C:2]1[C:3]([F:17])=[C:4]2[O:8][C:7]([CH:9]3[CH2:11][CH2:10]3)=[N:6][C:5]2=[C:12]([C:15]#[N:16])[C:13]=1[CH3:14].C([Sn](CCCC)(CCCC)[C:23]1[S:24][CH:25]=[CH:26][CH:27]=1)CCC.C(C1C(O)=C(C(C)(C)C)C=C(C)C=1)(C)(C)C>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:9]1([C:7]2[O:8][C:4]3[C:5](=[C:12]([C:15]#[N:16])[C:13]([CH3:14])=[C:2]([C:23]4[S:24][CH:25]=[CH:26][CH:27]=4)[C:3]=3[F:17])[N:6]=2)[CH2:11][CH2:10]1

Participants

6

Reactant 3

HCID 314042,6-Di-tert-butyl-4-methylphenolHCID 27793732-(Tri-n-butylstannyl)thiopheneHCID 510414276-Bromo-2-cyclopropyl-7-fluoro-5-methylbenzoxazole-4-carbonitrile

Product 1

HCID 685859762-Cyclopropyl-7-fluoro-5-methyl-6-(thiophen-2-yl)-1,3-benzoxazole-4-carbonitrileYield 96%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (200 mg, 0.68 mmol), 2-(tri-n-butylstannyl)thiophene (280 μl, 0.88 mmol) and 2,6-di-tert-butyl-p-cresol (2 grains) were dissolved in 1,4-dioxane (6 ml), and at room temperature, bis(triphenylphosphine)palladium(II) dichloride (48 mg, 0.07 mmol) was added. The solution was stirred under nitrogen atmosphere at 100° C. for 15 hours. After cooling to room temperature, the insoluble matter was separated by filtration with washing with ethyl acetate. The filtrate was washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, n-hexane:ethyl acetate=19:1, v/v) to obtain the entitled compound (194 mg, 96%) as a white solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe insoluble matter was separated by filtration
  3. washwith washing with ethyl acetate
  4. washThe filtrate was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe insoluble matter was separated by filtration
  7. customthe solvent was evaporated away
  8. customthe resulting residue was purified by middle-pressure liquid chromatography (eluent, n-hexane

Sources & evidence

ORD record
ord-c6b8eaf62198449dbc98ea4404329060
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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