Dimethylformamide → 4-[5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl]-2-methylbenzonitrile

HRID 216003Notes

Reaction equation

HRID 216003 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=2)=[CH:4][C:3]=1[CH3:25].[CH3:26][N:27](C)C=O>C1(C)C=CC=CC=1.[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:24][C:19]1[CH:18]=[C:17]([C:11]2([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([C:26]#[N:27])=[C:3]([CH3:25])[CH:4]=3)[CH2:12]2)[CH:22]=[C:21]([Cl:23])[CH:20]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 231598123-(4-Bromo-3-methylphenyl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole

Product 1

HCID 582001084-[5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl]-2-methylbenzonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

Zinc(II) cyanide (0.47 g) was added at ambient temperature to a solution of 3-(4-bromo-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole (3.0 g) (Example I4) in N,N-dimethylformamide (80 ml). Under an atmosphere of argon, tetrakis(triphenylphosphine) palladium(0) (0.46 g) was added. The mixture was heated to 115° C. for 27 hours. The reaction mixture was cooled to ambient temperature, diluted with toluene, washed with aqueous ammonium hydroxide (1M), then with brine, dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 4:1) to give 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzonitrile (2.26 g) as a white solid. 1H-NMR (CDCl3, 400 MHz): 7.65 (t, 2H), 7.57 (d, 1H), 7.5 (s, 1H), 7.42 (m, 2H), 4.08 (d, 1H), 3.7 (d, 1H), 2.58 (s, 3H) ppm.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. washwashed with aqueous ammonium hydroxide (1M)
  3. dry with materialwith brine, dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-c5afd0715392422f87a1fc0ee0a9fe09
Source dataset
uspto-grants-2012_06
Patent number
US08193221B2

Reaction notes

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