HCID 118431936, compound → HCID 118431946, compound

HRID 2208073Notes

Reaction equation

HRID 2208073 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH:12]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25](=[O:27])[CH3:26])=[CH:21][CH:20]=3)=[CH:15][C:14]=2[F:28])[CH2:11][C:10]([C:29]([C:35]([F:38])([F:37])[F:36])([C:31]([F:34])([F:33])[F:32])[OH:30])=[N:9]1.[CH3:39][Mg]Cl>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH:12]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:20]=[CH:21][C:22]([C:25]([OH:27])([CH3:39])[CH3:26])=[CH:23][CH:24]=3)=[CH:15][C:14]=2[F:28])[CH2:11][C:10]([C:29]([C:35]([F:38])([F:37])[F:36])([C:31]([F:32])([F:33])[F:34])[OH:30])=[N:9]1

Participants

4

Reactant 2

HCID 118431936HCID 118431936, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 118431946HCID 118431946, compoundYield 43.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of 1-(2-chloro-phenyl)-5-(4′-acetyl-3-fluoro-biphenyl-4-yl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole (10.0 mg, 0.02 mmol) prepared in Example 341 in tetrahydrofuran (1.0 mL), was slowly added methylmagnesium chloride (in 3.0 M tetrahydrofuran, 30.0 uL, 0.09 mmol) under nitrogen atmosphere at −78° C. The reaction mixture was stirred at −78° C. for 5 hours, quenched with a saturated solution of ammonium chloride at 0° C., and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/3) to give 5.0 mg of the titled compound as a yellow liquid.

Workup

  1. customat −78° C
  2. customquenched with a saturated solution of ammonium chloride at 0° C.
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with distilled water and brine
  5. dry with materialdried on anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a yellow liquid residue
  8. customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/3)

Sources & evidence

ORD record
ord-42d7664ac14b4d4a842bfc8357202dc5
Source dataset
uspto-grants-2016_06
Patent number
US09376420B2

Reaction notes

Loading…