Ethyl Acetate → HCID 89649544, compound

HRID 2207635Notes

Reaction equation

HRID 2207635 reaction equation
[CH3:1][N:2]1[C:6](B2OC(C)(C)C(C)(C)O2)=[CH:5][CH:4]=[N:3]1.[CH2:16]([O:23][C:24]1[CH:29]=[C:28](Br)[CH:27]=[CH:26][C:25]=1[F:31])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Na+].[Na+].CCOC(C)=O>CC#N.O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:16]([O:23][C:24]1[CH:29]=[C:28]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][CH:5]=2)[CH:27]=[CH:26][C:25]=1[F:31])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 73553470HCID 73553470, compound

Product 1

HCID 89649544HCID 89649544, compoundYield 74.8%

Reagents, catalysts & solvents 3

HCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (1058.42 mg, 5.09 mmol) in MeCN (40 mL) and water (10 mL) was added 2-benzyloxy-4-bromo-1-fluoro-benzene [CAS: 1036724-54-5](1300 mg, 4.62 mmol), sodium carbonate (1470.8 mg, 13.88 mmol) and bis(triphenylphosphine)palladium (II) dichloride (164.24 mg, 0.2300 mmol). The reaction was then heated at 100° C. for 4 hours. The cooled reaction mixture was poured into EtOAc (70 mL) and water (100 mL). The organics were separated, and washed with brine (75 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was then purified over silica (25 g, SNAP cartridge), eluting with EtOAc in isohexane from 0% to 40%. Fractions containing desired product were combined and concentrated in vacuo to give 5-(3-benzyloxy-4-fluoro-phenyl)-1-methyl-pyrazole (D82) (1026.5 mg, 3.4543 mmol, 74.7% yield) as a colourless oil;

Workup

  1. customThe cooled reaction mixture
  2. customThe organics were separated
  3. washwashed with brine (75 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was then purified over silica (25 g, SNAP cartridge)
  8. washeluting with EtOAc in isohexane from 0% to 40%
  9. additionFractions containing desired product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-049ca993559d415b96353671db0b42ad
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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