Water → HCID 68737131, compound

HRID 467940Notes

Reaction equation

HRID 467940 reaction equation
[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH2:14][C:13]([C:19]3[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=3)([C:15]([F:18])([F:17])[F:16])[O:12][N:11]=2)=[CH:6][C:5]=1Br.[Cu][C:30]#[N:31].[C:32](=O)([O-])[O-].[Na+].[Na+].O>CN(C)C=O>[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH2:14][C:13]([C:19]3[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=3)([C:15]([F:18])([F:17])[F:16])[O:12][N:11]=2)=[C:6]([CH3:32])[C:5]=1[C:30]#[N:31]

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 59563492HCID 59563492, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 68737131HCID 68737131, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of 2-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoic acid methyl ester (Example I13) (2.52 g) in dry N,N-dimethylformamide (75 ml) was added copper(I) cyanide (1.145 g). The reaction mixture was stirred at 160° C. for 40 minutes. The reaction mixture was allowed to cool to ambient temperature and was poured into a mixture of aqueous sodium carbonate (saturated) and water (1:2) (150 ml). The mixture was extracted with ethyl acetate (3×70 ml). The combined organic extracts were washed with water (2×70 ml) and brine (70 ml), dried over sodium sulfate and concentrated. The residue was re-crystallized from a mixture of diethyl ether and heptane (1:1) to give methyl 2-cyano-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoic acid methyl ester (1.474 g). 1H-NMR (CDCl3, 400 MHz): 8.23-7.45 (m, 6H), 4.11 (d, 1H), 4.03 (s, 3H), 3.74 (d, 1H).

Workup

  1. temperatureto cool to ambient temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×70 ml)
  3. washThe combined organic extracts were washed with water (2×70 ml) and brine (70 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was re-crystallized from a mixture of diethyl ether and heptane (1:1)

Sources & evidence

ORD record
ord-4de141986194424fa4746bcafc5dfdf9
Source dataset
uspto-grants-2014_01
Patent number
US08623896B2

Reaction notes

Loading…