Ethanol → HCID 118431687, compound

HRID 2208082Notes

Reaction equation

HRID 2208082 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[F:20])[N:11]=[C:10]([C:21]([C:27]([F:30])([F:29])[F:28])([C:23]([F:26])([F:25])[F:24])[OH:22])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:31][S:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1.C(O)C.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[F:20][C:14]1[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:13]=1[N:12]1[CH:8]([C:5]2[CH:6]=[CH:7][C:2]([C:37]3[CH:36]=[CH:35][CH:34]=[C:33]([S:32][CH3:31])[CH:38]=3)=[CH:3][CH:4]=2)[CH2:9][C:10]([C:21]([C:27]([F:29])([F:30])[F:28])([C:23]([F:25])([F:26])[F:24])[OH:22])=[N:11]1

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343833-(Methylthio)benzeneboronic acidHCID 118431708HCID 118431708, compound

Product 1

HCID 118431687HCID 118431687, compoundYield 11.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
88 °C

Procedure

5-(4-Bromo-phenyl)-1-(2,4-difluoro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole (50.0 mg, 0.10 mmol) prepared in Step 2 of Preparation 22, 3-(methylthio)-phenylboronic acid (25.0 mg, 0.15 mmol), Pd(PPh3)4 (11.5 mg, cat.), ethanol 0.5 mL and a 2N sodium carbonate solution (0.5 mL) were added to 1,2-dimethoxyethane (2.0 mL). The reaction mixture was stirred at 88° C. for 2 hours and then filtered through celite pad. A saturated solution of ammonium chloride was added to the filtrate, which was then extracted with ethyl acetate three times. The combined extract was washed with 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=1/10) to give 6.1 mg of the titled compound as a yellow liquid.

Workup

  1. filtrationfiltered through celite pad
  2. additionA saturated solution of ammonium chloride was added to the filtrate, which
  3. extractionwas then extracted with ethyl acetate three times
  4. extractionThe combined extract
  5. washwas washed with brine
  6. dry with materialdried on anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto give a yellow liquid residue
  9. customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/10)

Sources & evidence

ORD record
ord-a37b8c73d50b491693620b99fbb10b6f
Source dataset
uspto-grants-2016_06
Patent number
US09376420B2

Reaction notes

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