2,6-Di-tert-butyl-4-methylphenol → 4-cyano-6-[1-(ethoxy)ethenyl]-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide

HRID 17394

Reaction equation

HRID 17394 reaction equation
Br[C:2]1[C:15]([CH3:16])=[C:14]([C:17]#[N:18])[C:5]2[N:6]=[C:7]([C:9]([N:11]([CH3:13])[CH3:12])=[O:10])[O:8][C:4]=2[C:3]=1[F:19].C([Sn](CCCC)(CCCC)[C:25]([O:27][CH2:28][CH3:29])=[CH2:26])CCC.C(C1C(O)=C(C(C)(C)C)C=C(C)C=1)(C)(C)C>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.C1(C)C=CC=CC=1>[C:17]([C:14]1[C:5]2[N:6]=[C:7]([C:9]([N:11]([CH3:13])[CH3:12])=[O:10])[O:8][C:4]=2[C:3]([F:19])=[C:2]([C:25]([O:27][CH2:28][CH3:29])=[CH2:26])[C:15]=1[CH3:16])#[N:18]

Participants

6

Reactant 3

HCID 314042,6-Di-tert-butyl-4-methylphenolHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 685849626-Bromo-4-cyano-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide

Product 1

HCID 685850534-cyano-6-[1-(ethoxy)ethenyl]-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamideYield 81.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolvent

Procedure

Under nitrogen atmosphere, bis(triphenylphosphine)palladium chloride (435 mg, 620 μmol) was added to a toluene (125 ml) solution of 6-bromo-4-cyano-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide (I-127) (4.04 g, 12.4 mmol), tributyl(1-ethoxyvinyl)tin (5.37 g, 14.9 mmol) and 2,6-di-tert-butyl-p-cresol (about 20 grains), and heated under reflux for 20 hours. After cooling, the solvent was evaporated away under reduced pressure, then n-hexane was added to the resulting residue and stirred at room temperature for 1 hour. Next, the precipitated solid was collected by filtration and subjected to silica gel column chromatography, and the eluate with n-hexane/ethyl acetate (1:1, v/v) gave 4-cyano-6-[1-(ethoxy)ethenyl]-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide (3.20 g, 81%) as a yellow solid. The fraction containing impurities was recovered and purified in the same manner, and 3.57 g (91%) of 4-cyano-6-[1-(ethoxy)ethenyl]-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide was obtained in total. The analytical data are shown below.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 20 hours
  3. temperatureAfter cooling
  4. customthe solvent was evaporated away under reduced pressure
  5. additionn-hexane was added to the resulting residue
  6. filtrationNext, the precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-3d5d90e362c14136b65522860ec53418
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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