Dimethylformamide → 5-(2'-acetyl-biphenyl-3-yl)-1-(2-chloro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole

HRID 2208044Notes

Reaction equation

HRID 2208044 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[N:11]=[C:10]([C:20]([C:26]([F:29])([F:28])[F:27])([C:22]([F:25])([F:24])[F:23])[OH:21])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[C:30]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1B(O)O)(=[O:32])[CH3:31].C(=O)([O-])[O-].[Na+].[Na+].CN(C)C=O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(OCC)(=O)C>[C:30]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[N:11]=[C:10]([C:20]([C:22]([F:23])([F:25])[F:24])([C:26]([F:29])([F:27])[F:28])[OH:21])[CH2:9]2)[CH:3]=1)(=[O:32])[CH3:31]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27343092-Acetylphenylboronic acidHCID 1184321755-(3-Bromo-phenyl)-1-(2-chloro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole

Product 1

HCID 1184317655-(2'-acetyl-biphenyl-3-yl)-1-(2-chloro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazoleYield 23.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

5-(3-Bromo-phenyl)-1-(2-chloro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole (20.0 mg, 0.04 mmol) prepared in Step 4 of Preparation 16, 2-acetylphenylboronic acid (8.0 mg, 0.05 mmol), Pd(dppf)Cl2 (2.0 mg, cat.), and a 2N sodium carbonate solution (0.5 mL) were added to N,N-dimethylformamide (0.5 mL). The reaction mixture was stirred at 80° C. for 16 hours and then ethyl acetate was added thereto. The reaction mixture 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=1/2) to give 5.0 mg of the titled compound as a yellow liquid.

Workup

  1. washThe reaction mixture was washed with distilled water and brine
  2. dry with materialdried on anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto give a yellow liquid residue
  5. customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/2)

Sources & evidence

ORD record
ord-ee52e76b2ee04f0081e9ee3978d7c190
Source dataset
uspto-grants-2016_06
Patent number
US09376420B2

Reaction notes

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