Ammonium Chloride → 2-Cyclopropyl-7-fluoro-6-(3-fluorophenyl)-5-methyl-1,3-benzoxazole-4-carbonitrile

HRID 17448

Reaction equation

HRID 17448 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].[F:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl-].[NH4+]>O1CCOCC1.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.C(OCC)(=O)C>[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[CH:22]=[CH:21][CH:20]=[C:19]([F:18])[CH:24]=4)[C:3]=3[F:17])[N:6]=2)[CH2:11][CH2:10]1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 27339863-Fluorophenylboronic acidHCID 510414276-Bromo-2-cyclopropyl-7-fluoro-5-methylbenzoxazole-4-carbonitrile

Product 1

HCID 685871562-Cyclopropyl-7-fluoro-6-(3-fluorophenyl)-5-methyl-1,3-benzoxazole-4-carbonitrileYield 72%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (200 mg, 0.68 mmol), 3-fluorophenylboronic acid (380 mg, 2.71 mmol) and tripotassium phosphate (288 mg, 1.36 mmol) were dissolved in 1,4-dioxane (8 ml), then at room temperature, tetrakis(triphenylphosphine)palladium(0) (157 mg, 0.14 mmol) was added. The solution was stirred under nitrogen atmosphere at 95° C. for 17 hours. After cooling to room temperature, the reaction liquid was fractionated with ethyl acetate and aqueous saturated ammonium chloride solution. The aqueous layer was further 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=8:1) to obtain the entitled compound (151 mg, 72%) as a white solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction liquid
  3. extractionThe aqueous layer was further extracted twice with ethyl acetate
  4. washwashed 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, hexane:ethyl acetate=8:1)

Sources & evidence

ORD record
ord-4483e468c3ee43868833523ca3ced70d
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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