HCID 71138340, compound → HCID 71138338, compound

HRID 587292Notes

Reaction equation

HRID 587292 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 aqueous NH4Cl solution and extracted with EtOAc. 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 aqueous NH4Cl solution
  2. extractionextracted with EtOAc
  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-e8ade44c14704b57a2b2b0acffe3aa3e
Source dataset
uspto-grants-2016_01
Patent number
US09226500B2

Reaction notes

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