Dimethylformamide → 5-Fluoropyridine-2-carboxamide

HRID 130814Notes

Reaction equation

HRID 130814 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.C([Cu])#N.C[N:13]([CH:15]=[O:16])C>Cl>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:15]([NH2:13])=[O:16])=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 27831712-Bromo-5-fluoropyridineHCID 178418546HCID 178418546, compound

Product 1

HCID 219047545-Fluoropyridine-2-carboxamideYield 31.2%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
100 °C

Procedure

Take up 2-bromo-5-fluoropyridine (0.750 g, 4.26 mmol) and CuCN (0.954 g, 10.7 mmol) in DMF (10.7 mL). Heat to reflux for 5 hours. Cool the reaction mixture to 100° C. Add a solution of FeCl36H2O (0.654 g) in 10% HCl solution (30 mL) and stir for 15.5 hours. Cool the reaction mixture to 80° C. and filter. Add 1.0 N NaOH until the reaction mixture becomes basic and extract with dichloromethane (3×200 mL). Wash the organic layer with brine (1×75 mL), dry over Na2SO4, filter and concentrate to give the title compound (0.186 g, 31.2%): TOF MS EI+ 140.0 (M)+, base peak EI+ 97.0 (M−CONH)+, HRMS calcd for C6H5N2OF 140.0386, found 140.0378, time 3.40 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 30-99% over 19 min], tR=7.5 min, 100% purity.

Workup

  1. temperatureHeat
  2. temperatureto reflux for 5 hours
  3. temperatureCool the reaction mixture to 80° C.
  4. filtrationfilter
  5. additionAdd 1.0 N NaOH until the reaction mixture
  6. extractionextract with dichloromethane (3×200 mL)
  7. washWash the organic layer with brine (1×75 mL)
  8. dry with materialdry over Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-9ba5a4face824a0ab512f05755a7a699
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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