2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → 2-Fluoro-5-methoxy-4-(2-methyl-1,3-oxazol-5-yl)benzonitrile

HRID 71191Notes

Reaction equation

Cl[C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[O:13][C:12]([CH3:14])=[N:11][CH:10]=2)=[C:4]([O:15][CH3:16])[CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=C[C:31]=2[N:36](C)C)CCCCC1>CN(C=O)C.O.[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:8][C:7]1[CH:6]=[C:5]([C:9]2[O:13][C:12]([CH3:14])=[N:11][CH:10]=2)[C:4]([O:15][CH3:16])=[CH:3][C:2]=1[C:31]#[N:36]

Participants

Conditions

Temperature: 130 °C

Procedure

To a mixture of 5-(4-chloro-5-fluoro-2-methoxyphenyl)-2-methyl-1,3-oxazole (1.12 g) and zinc(II) cyanide (0.327 g) in DMF (10 mL) were added tris(dibenzylideneacetone)dipalladium(0) (212 mg) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (182 mg) at room temperature, and the mixture was stirred overnight under a nitrogen atmosphere at 130° C. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (902 mg).

Workup

extractionthe mixture was extracted with ethyl acetate
washThe extract was washed with water and saturated brine
dry with materialdried over anhydrous magnesium sulfate
customthe solvent was evaporated under reduced pressure
customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record: ord-abde0950e4da4af39860badb28f3502b
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822699B2

Reaction notes

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