Potassium Carbonate → HCID 60026537, compound

HRID 400655Notes

Reaction equation

HRID 400655 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:11]([CH3:20])([CH3:19])[CH2:12][C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1.[N:21]1[CH:26]=[C:25](B(O)O)[CH:24]=[N:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>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.CO.COCCOC.CN(C=O)C>[F:15][C:14]([F:17])([F:16])[C:13](=[O:18])[CH2:12][C:11]([CH3:20])([C:4]1[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=[C:2]([C:25]2[CH:26]=[N:21][CH:22]=[N:23][CH:24]=2)[CH:3]=1)[CH3:19]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 223986074-(5-Bromo-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-one

Product 1

HCID 60026537HCID 60026537, compoundYield 63.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86594022DME MeOH DMFSolvent

Procedure

To a mixture of 4-(5-bromo-2,3-dihydrobenzofuran-7-yl)-1, 1,1-trifluoro-4-methylpentan-2-one (1.00 g, 2.8 mmol), pyrimidine-5-boronic acid (529 mg, 4.3 mmol) and potassium carbonate (787 mg) in a sealed tube was added 20 mL of MeOH-DME-DMF (3:2:1). After stirring at room temperature for 10 minutes, tetrakis(triphenylphosphine)palladium(0) (329 mg) was added and the reaction mixture was heated at 120° C. for 40 minutes. After cooling to room temperature, the crude mixture was filtered through a cotton plug with the aid of ethyl acetate. The filtrate was concentrated in vacuo to remove most of the methanol, redissolved in 160 mL of ethyl acetate, and washed with 80 mL of aqueous 1 N sodium hydroxide solution, 80 mL of water, and 80 mL of brine respectively. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography with 20% to 30% ethyl acetate-hexanes afforded 620 mg (62% yield) of the title compound.

Workup

  1. temperaturethe reaction mixture was heated at 120° C. for 40 minutes
  2. temperatureAfter cooling to room temperature
  3. filtrationthe crude mixture was filtered through a cotton plug with the aid of ethyl acetate
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto remove most of the methanol
  6. dissolutionredissolved in 160 mL of ethyl acetate
  7. washwashed with 80 mL of aqueous 1 N sodium hydroxide solution, 80 mL of water, and 80 mL of brine respectively
  8. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by column chromatography with 20% to 30% ethyl acetate-hexanes

Sources & evidence

ORD record
ord-d88e645785534885a69b8908fc996131
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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