HCID 71138340, compound → HCID 71138338, compound

HRID 1503776Notes

Reaction equation

HRID 1503776 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([C:12](=[O:27])[CH2:13][CH:14]([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])=[CH:8][CH:7]=2)[CH:5]=[N:4][CH:3]=[N:2]1.[CH3:28][Mg]Br>C1COCC1>[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([C:12]([OH:27])([CH2:13][CH:14]([C:19]3[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=3)[C:15]([F:18])([F:16])[F:17])[CH3:28])=[CH:10][CH:11]=2)[CH:5]=[N:4][CH:3]=[N:2]1

Participants

4

Reactant 2

HCID 71138340HCID 71138340, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 71138338HCID 71138338, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobutan-1-one (300 mg, 0.726 mmol) in THF cooled to 0° C. was added methylmagnesium bromide (450 mg, 5 mmol) drop wise. The reaction was stirred for 3 h at 0° C., then the reaction mixture was quenched with sat aq NH4Cl solution and extracted with ethyl acetate. The combined EtOAc layer was washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography (SiO2, 100-200 mesh; 20%-25% EtOAc in petroleum ether) afforded the title compound as a solid (100 mg, 32%): 1H NMR (400 MHz, CDCl3) δ two diastereoisomers 8.58 (s, 1H, minor), 8.48 (s, 1H, major), 8.13 (s, 1H, minor), 8.09 (s, 1H, major), 7.70 (d, J=9.0 Hz, 2H, minor), 7.53 (d, J=9.0 Hz, 2H, minor), 7.40 (d, J=9.0 Hz, 2H, major), 7.31 (m, 1H, minor), 7.27 (d, J=9.0 Hz, 2H, major), 7.20 (m, 2H, minor), 7.01 (m, 1H, major), 6.75 (m, 2H, major), 350 (m, 1H), 2.50 (m, 2H), 1.56 (s, 3H, major), 1.54 (s, 3H, minor); ESIMS m/z 430.05 ([M+H]+).

Workup

  1. customthe reaction mixture was quenched with sat aq NH4Cl solution
  2. extractionextracted with ethyl acetate
  3. washThe combined EtOAc layer was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification by column chromatography (SiO2, 100-200 mesh; 20%-25% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-1070970c14d44b0181afe834eea3d893
Source dataset
uspto-grants-2015_12
Patent number
US09212164B2

Reaction notes

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