5-Bromo-3-fluoropyridine-2-carbonitrile → 5-Cyclopropyl-3-fluoropicolinonitrile

HRID 571688Notes

Reaction equation

HRID 571688 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:10])[C:5]([C:8]#[N:9])=[N:6][CH:7]=1.[Br-].[CH:12]1([Zn+])[CH2:14][CH2:13]1>C1COCC1.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>[CH:12]1([C:2]2[CH:3]=[C:4]([F:10])[C:5]([C:8]#[N:9])=[N:6][CH:7]=2)[CH2:14][CH2:13]1

Participants

5

Reactant 2

HCID 441966805-Bromo-3-fluoropyridine-2-carbonitrileHCID 178419765HCID 178419765, compound

Product 1

HCID 670860995-Cyclopropyl-3-fluoropicolinonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To solution of 5-bromo-3-fluoropicolinonitrile (603 mg, 3.0 mmol) and Pd(PPh3)4 (173 mg, 0.15 mmol) in 10 mL of THF was added cyclopropyl zinc bromide (0.5 M, 10 mL) under N2. After being heated 80° C. for 4 h, the mixture was cooled to room temperature and quenched with sat. NH4CL (aq). The mixture was extracted with EtOAc (3×) and the combined organic layers were washed with sat. NaHCO3 (aq.) and brine, dried (MgSO4), and concentrated. The crude product was purified by silica gel chromatography (elution with 0-8% EtOAc/Hex) to afford 5-cyclopropyl-3-fluoropicolinonitrile (406 mg).

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. customquenched with sat. NH4CL (aq)
  3. extractionThe mixture was extracted with EtOAc (3×)
  4. washthe combined organic layers were washed with sat. NaHCO3 (aq.) and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography (elution with 0-8% EtOAc/Hex)

Sources & evidence

ORD record
ord-cdcb624f93a7479b961cdca397d832e3
Source dataset
uspto-grants-2015_05
Patent number
US09029362B2

Reaction notes

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