Potassium Carbonate → HCID 44816051, compound

HRID 631021Notes

Reaction equation

HRID 631021 reaction equation
Br[C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[CH2:4][N:5]([CH:16]1[CH2:18][CH2:17]1)[C:6]([C:8]1[C:9]([CH3:15])=[N:10][N:11]([CH3:14])[C:12]=1[F:13])=[O:7].[C:23]1(B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[C:32](=O)([O-])[O-].[K+].[K+].CCCCCCC.C(OCC)(=O)C>O1CCCC1.O.[Cl-].[Na+].O.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>[C:2]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[CH:4]([N:5]([CH:16]1[CH2:18][CH2:17]1)[C:6]([C:8]1[C:9]([CH3:15])=[N:10][N:11]([CH3:14])[C:12]=1[F:13])=[O:7])[CH3:32]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 21899848Ethylacetate heptaneHCID 67071781HCID 67071781, compound

Product 1

HCID 44816051HCID 44816051, compoundYield 73.9%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 300 mg (0.789 mmol) of N-(2-bromobenzyl)-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide in 10 ml of tetrahydrofurane are successively added 120 mg (0.986 mmol) of phenylboronic acid, 163 mg (1.183 mmol) of potassium carbonate dissolved in 5 ml of water and 9 mg (0.01 equivalent) of tetrakis(triphenylphosphine)palladium. The reaction mixture is heated at 80° C. for 4 hrs. The reaction mixture is then cooled to ambient temperature and poured on 50 ml of brine. The watery layer is extracted three times with diethyl ether and the combined organic layers are successively washed by a 1M solution of sodium hydroxide, brine and filtered over a phase separator filter to yield after concentration 310 mg of a brown oil. Column chromatography (gradient heptane/ethyl acetate) yielded 220 mg (68% yield) of N-[1-(biphenyl-2-yl)ethyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide as a white solid; melting point [mp]=100° C.

Workup

  1. temperatureThe reaction mixture is then cooled to ambient temperature
  2. extractionThe watery layer is extracted three times with diethyl ether
  3. washthe combined organic layers are successively washed by a 1M solution of sodium hydroxide, brine
  4. filtrationfiltered over a phase separator
  5. filtrationfilter
  6. customto yield after concentration 310 mg of a brown oil

Sources & evidence

ORD record
ord-8f4c338c53a34ed08cdb0c96471ca7fb
Source dataset
uspto-grants-2016_04
Patent number
US09320277B2

Reaction notes

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