Ethyl Acetate → 6-(3-Aminophenyl)-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

HRID 17455Notes

Reaction equation

HRID 17455 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].O.[NH2:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.[Cl-].[Na+].O.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>[NH2:19][C:20]1[CH:25]=[C:24]([C:2]2[C:3]([F:17])=[C:4]3[O:8][C:7]([CH:9]4[CH2:11][CH2:10]4)=[N:6][C:5]3=[C:12]([C:15]#[N:16])[C:13]=2[CH3:14])[CH:23]=[CH:22][CH:21]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 143894233-Aminophenylboronic acid monohydrateHCID 510414276-Bromo-2-cyclopropyl-7-fluoro-5-methylbenzoxazole-4-carbonitrile

Product 1

HCID 685845026-(3-Aminophenyl)-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
95 °C

Procedure

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (150 mg, 0.51 mmol) and 3-aminophenylboronic acid monohydrate (315 mg, 2.03 mmol) were dissolved in 1,4-dioxane (5 ml), then at room temperature, tripotassium phosphate (216 mg, 1.02 mmol) and then tetrakis(triphenylphosphine)palladium(0) (118 mg, 0.10 mmol) were added. The suspension was stirred under nitrogen atmosphere at 95° C. for 12 hours. After cooling to room temperature, the solution was fractionated with ethyl acetate and saturated brine. The aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, 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, hexane:ethyl acetate=2:1) to obtain the entitled compound (170 mg, quant.) as a white amorphous substance.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous layer was extracted twice with ethyl acetate
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe insoluble matter was separated by filtration
  6. customthe solvent was evaporated away
  7. customthe resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=2:1)
  8. customto obtain the entitled compound (170 mg, quant.) as a white amorphous substance

Sources & evidence

ORD record
ord-d11ffddaf3f24e7a8e432e8d3f6df520
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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